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AFM in Nano-Biomechanics (October Journal Club Topic)

Majid Minary's picture


The October 2011 journal club theme is "AFM in Nano-biomechanics". Nano-biomechanics is an emerging field that aims at exploring fundamental science and engineering related to biological materials at the nanoscale ( and Atomic force microscope (AFM) has been one of the instrumental tools in this field by providing pN force sensitivity, and better than nanometer spatial resolution.

AFM was originally developed to overcome the limitations of the scanning tunneling microscope (STM) in high-resolution imaging of insulating materials. Utilizing a sharp tip (~10-20 nm in radius of curvature) on a micro-fabricated cantilever, AFM uses short range repulsive forces and long range attractive forces between the probe tip and the sample to image the surface topography with better than nanometer resolution. AFM was initially intended for solid-state martial characterization. However, the ability to function under gentle forces (essential for soft biological materials) as well as its extension to operate under liquid environment (compatible with physiological condition) rendered AFM as a powerful and indispensable tool in bioscience. The promise that AFM can provide imaging resolutions (~nm) beyond that of the diffraction-limited resolution of the optical microscope (~200 nm) presented AFM as a complementary tool in biological tool-box.

Most of the applications of AFM are achieved through modification of the cantilever (probe) in order to attain the desired function. This Journal Club summarizes exciting applications of AFM in various forms applied to biomaterials ranging from basic imaging, to nanomechanics including nanoindentation and cell mechanics, viscoelastic characterization and local strain mapping. Most of the applications would certainly require expertise from mechanics community in terms of modeling and experimentations. This discussion is intended to stimulate involvement of the community in these exciting and emerging fields, by giving examples and presenting potential areas for new contributions. Figure 1 summarizes several of the main functions of AFM on biomaterials, which is achieved mainly through the modification of the probe to achieve specific objectives. The list is by no means comprehensive. It is intended that through discussion we can add to the list. Approaching the end of the month, I intend to summarize the discussions and add any new references suggested from research within various groups. 


AFM application in Nano-Biomechanics

 Fig. 1: Schematic of the several applications of AFM in biomaterials. (a) high-resolution imaging of cortical bone and individual collagen fibril (inset); (b) measurement of viscoelastic and rate- dependent properties of individual living cells; (c) characterization of electro-mechanical coupling in individual collagen fibrils; (d) mapping the local strain field in situ tensile experiments; (e) penetration of living cell membrane by a nanoneedled-probe; and (f) nano-injection of living cells by local rupture of the cell membrane for drug delivery at the single-cell level.




1. High-resolution imaging
The most common application of AFM on biomaterials is the high-resolution imaging (Fig. 1a). For imaging purposes, AFM cantilever is in its most basic form, i.e. a sharp tip with a radius of curvature below ~20 nm in order to achieve high lateral resolution. More frequently, high resolution imaging is obtained in the so-called tapping mode, where the AFM cantilever oscillates near its resonance frequency for enhanced sensitivity. High resolution images of many biomaterials such as individual collagen fibrils, cortical bone, living cells, and various proteins have been presented in the literature. Imaging function of AFM in air is straightforward. However, imaging in liquid environment, which is the desired environment for biomaterials, encounters major difficulties. This is due to the low quality factor of the oscillating probe caused by the large hydrodynamic drag in interaction with the surrounding liquid. Concepts of mechanical vibrations and the fundamentals of fluid mechanics concerning a vibrating object in a viscous medium would prove important in achieving a solution for this problem.

2. Nanoindentation, viscoelasticity, and cell mechanics
Obtaining local mechanical properties of the often heterogeneous and viscoelastic biomaterials is of particular interest. In nanoindentation function, AFM tip is pressed against the surface and the corresponding force to the applied deformation is measured with pico-Newton accuracy. This method has been applied to study nanomechanical heterogeneity in bone, in collagen fibril, for study cancer cells and also for early detection of osteoarthritis. An extension of the nanoindentation is in measuring viscoelastic properties of living cells (Fig. 1b). For this case usually a spherical micro-sphere is glued onto the distal end of the AFM cantilever in order to avoid damage to the cell membrane caused by a sharp tip and to probe an average representative structure of the otherwise heterogeneous cytoskeleton of the cell. In order to obtain the time-dependent viscoelastic properties of the cell, a dynamic deformation is applied to the cell with a certain amplitude and frequency. The amplitude and the phase shift between the applied deformation and the resulting force are analyzed to extract the viscoelastic mechanical properties of the cell structure. Most often the nanoindentation problems are modeled using contact mechanics principles. Most of the current contact mechanics models are for (quasi-) static interactions between two homogenous elastic bodies. There is still plenty of room for improvement in modeling indentation problems of heterogeneous and viscoelastic materials, to resemble true interaction of the AFM probe and the living cells, extracellular matrix and other biological materials.

3. Electromechanical coupling (piezoelectricity)
Characterization of the local electromechanical coupling in biomaterials at the nanoscale requires application of a local electric field on the sample and measurement of small (often several pico-meters) deformation induced by the electric field. Piezoresponse force microcopy (PFM) is a powerful method based on AFM that measures the converse piezoelectric effect with a nm in-plane resolution (Fig. 1c). In this method, a harmonic electric field is applied between a conductive AFM cantilever and the material of interest mounted on an often grounded substrate. Piezoelectricity in cortical bone, individual collagen fibrils, and peptide proteins has been reported in the literature. For biological materials, the piezoelectricity, although very small (several pm/V range), has been proposed to have significant effect in their mechanobiology and remodeling. There was an interesting and comprehensive journal club discussion on this subject in May in imechanica that could be referred to for further information.

4. Local strain mapping
Stress-strain relationship is a fundamental characteristic of a material, which is conventionally obtained by the simple tension experiment. Stress is obtained from the applied load and the strain is often calculated from the total displacement of the gauge length. Local strain in the material could be inhomogeneous and different than the global strain. One powerful method based on the AFM is the simultaneous tensile test and AFM imaging (in situ AFM tension). In this method, which has been successfully applied to realize deformation mechanism in nacre, a micro-tensile stage is placed under the AFM probe. At each step of deformation, the gauge length of the sample is imaged with AFM with nm resolution (Fig. 1d). Digital Image correlation between the consecutive images from different steps is used to obtain the local strain and the deformation mechanism in the specimen of interest. This method could be extended to study deformation mechanism in particularly heterogeneous biomaterials such as tendon and bone and in fracture mechanics problems related to the crack tip growth. Knowledge about the local deformation mechanism could help in design of future biomimetic materials for high performance applications.

5. Nanoinjection and drug delivery at the single cell level
Local delivery of drugs and nano-particles into the cell cytosol requires gentle local rupture of the cell membrane with minimal damage and precise force control. The common microinjection methods using a glass pipette imposes large forces on the cell membrane, yielding to low cell viability. In recent years modified AFM probes are presented that could introduce external materials through the cell membrane with minimal invasiveness to the cells. Nanoneedled-probes, through fabrication of a small diameter nanoneedle on the AFM cantilever have been shown to be able to penetrate and deliver small number of bio-molecules or nano-particles across the cell membrane (Fig. 1e). For continuous delivery of larger volumes of drugs and bio-molecules fluidic probes are introduced that combine an on-chip micro-fluidic channel within a cantilever with a nano-fountain tip (Fig. 1f). These probes have been shown to be able to inject drugs into living cells with minimal damage through delicate force control enabled by AFM. Several outstanding problems that could be addressed by mechanics community in this regard include the penetration mechanism of different types of probes into the cell membrane (unmodified AFM tip vs. sharp nanoneedles), and the local stiffness of the cell membrane.


1. Cross, S.E., Y.-S. Jin, J. Rao and J.K. Gimzewski, Nanomechanical analysis of cells from cancer patients. Nature Nanotechnology, 2007. 2: p. 780 - 783.
2. Tai, K., M. Dao, S. Suresh, A. Palazoglu and C. Ortiz, Nanoscale heterogeneity promotes energy dissipation in bone. Nature Materials, 2007. 6: p. 454-462.
3. Stolz, M., R. Gottardi, R. Raiteri, S. Miot, I. Martin, R. Imer, U. Staufer, A. Raducanu, M. Düggelin, W. Baschong, A.U. Daniels, N.F. Friederich, A. Aszodi and U. Aebi, Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy. Nature Nanotechnology, 2009. 4: p. 186-192.
4. Kis, A., S. Kasas, B. Babic, A.J. Kulik, W. Benoit, G.A.D. Briggs, C. Scho¨nenberger, S. Catsicas and L. Forro, Nanomechanics of microtubules. Physical Review Letters, 2002. 89: p. 248101-4.
5. O. Loh, R. Lam, M. Chen, N. Moldovan, H. Huang, D. Ho, and H.D. Espinosa, "Nanofountain-Probe-Based High-Resolution Patterning and Single-Cell Injection of Functionalized Nanodiamonds," Small, 5, 1667(2009)
6. M. Minary-Jolandan and M.-F. Yu, "Uncovering Nanoscale Electromechanical Heterogeneity in the Subfibrillar Structure of Collagen Fibrils Responsible for the Piezoelectricity of Bone", ACS Nano 3, 1859 (2009).
7. Ikuo Obataya, Chikashi Nakamura, SungWoong Han, Noriyuki Nakamura, and Jun Miyake, Nanoscale Operation of a Living Cell Using an Atomic Force Microscope with a Nanoneedle, Nano Letters 2005, 5, 27 (2005).
8. M. Minary-Jolandan and M.-F. Yu, "Nanomechanical Heterogeneity in the Gap and Overlap Regions of Type I Collagen Fibrils with Implications for Bone Heterogeneity", Biomacromolecules 10, 2565 (2009).
9. X. Li, Z.-H. Xu, and R. Wang, "In-situ Observation of Nanograin Rotation and Deformation in Nacre," Nano Letters, 6 (2006) 2301-2304.
10. R. E. Mahaffy, C. K. Shih, F. C. MacKintosh, J. Käs, Scanning Probe-Based Frequency-Dependent Microrheology of Polymer Gels and Biological Cells, Physical Review Letters 85, 880 (2000).
11. Espinosa HD, Juster AL, Latourte FJ, Loh OY, Gregoire D, Zavattieri PD. Tablet-level origin of toughening in abalone shells and translation to synthetic composite materials. Nat Commun 2011;2:173.
12. X. Li, I. Chasiotis, and T. Kitamura, "In situ Scanning Probe Microscopy Nanomechanical Testing," MRS Bulletin, 35 (2010) 361-367.
13. O. Chaudhuri, S.H. Parekh, W.A. Lam, D.A. Fletcher, Combined atomic force microscopy and side-view optical imaging for mechanical studies of cells, Nature Methods, vol. 6(5), 383-387, 2009
14. T. Hassenkam, G.E. Fantner, J.A. Cutroni, J.C. Weaver, D.E. Morse, P.K. Hansma, High Resolution AFM Imaging of Intact and Fractured Trabecular Bone, Bone (July 2004), Vol. 35 (1): 4-10
15. Q. S. Li, G. Y. Lee, C.N. Ong and C.T. Lim, AFM indentation study of breast cancer cells. Biochem Biophys Res Commun., 2008. 374: p. 609.



Xiaodong Li's picture

Thanks Majid for posting this topic. AFM is unique with both imaging and manipulating functions. Recently, my group (Dr. Zhi-Hui Xu) used AFM to in situ image and probe the mechanical properties of the biopolymer nanostrands. The paper reports that the biopolymer in nacre can strength itself in deformation. For details, please see the following paper.

Zhi-Hui Xu and Xiaodong Li, Deformation Strengthening of Biopolymer in Nacre, Advanced Functional Materials, 2011, DOI: 10.1002/adfm.201100167

Majid Minary's picture

Hi Chris,

This is indeed an interesting and very relevant study. Thanks for posting. 

Nature often designs superior materials. Through delicate nanomechanics techniques one can learn the design principles in natural materials

and utilize them for designing tough and strong bioinspired synthetic materials.



Hi, Majid. Thank you for your nice introduction of AFM-based characterization of biological materials such as cells and tissues. I believe that AFM imaging and indentation (or single-molecule mechanics) are very useful in characterizing the surface of cells and tissues for further analysis, for instance, measuring the stiffness of cells (as mentioned by Majid).

However, I think that AFM imaging is also useful in sensing and detecting the biomolecular interactions at high resolution (even single-molecule resolution) for future applications such as early diagnosis of diseases such as cancers. For instance, Sahin and colleagues have introduced the novel AFM imaging (based on mechanical indentation) that is able to probe the imaging of a single DNA/RNA molecule [1]. Moreover, recent studies [2, 3] have shown that Kelvin probe force microscopy (KPFM) may enable the high-resolution imaging of biomolecular interactions. The principle of  KPFM is attributed to Lord Kelvin, who suggested the capacitance vibration method, where the surface potential difference between AFM tip and sample can be measured from a force acting on AFM tip when an ac electric field is used to drive the vibration of AFM tip [4]. We have reported the KPFM-based single-molecule recognition of the interaction between an individual kinase and ATP molecule (or drug molecule) [5]. As far as I know, AFM-based imaging of a single-molecule has recently received the attention from a community due to its ability to provide the detailed insight into various biomolecular interactions at high resolution. There might be still many rooms for researchers to make contribution to understanding the biomolecular interactions (for diagnosis or drug-screening) using AFM imaging and mechanics.


[1] Husale, et. al., Nature 462, p1075-1078 (2009)

[2] Sinensky, and Belcher, Nat. Nanotechnol. 2, p653-659 (2007)

[3] Leung, et. al., Nano Lett. 9, p2769-2773 (2009)

[4] Nonnenmacher, et. al., Appl. Phys. Lett. 58, p2921-2923 (1991)

[5] Park, et. al., ACS Nano 5, p6981-6990 (2011)   


Majid Minary's picture

Hi Kilho,

Thanks for sharing the papers. Single Molecule detection using AFM, particularly using coupled phenomena such as electrostatic field, as it is the case in Kelvin Probe Force Microscopy, adds whole new dimension to AFM-based biomechanics.  

I am glad that you brought up this topic. As many of AFM applications start with solid state materials, it is always nice to see their applications to bio-materials. In my summary at the end of the month, I will add a section of this topic, based on the papers you suggested. 


Xin Tang's picture



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Dear Majid,


Thanks for initiating this very
important topic. In addition to the essential functions and applications raised
by previous posts, AFM also possesses tremendous amount of potential in solving
many challenging questions in cell mechanics field. Here I would like to propose
one direction.


Thanks to its flexible force-measurement capability
in aqueous environment, AFM can been used to “touch” living cells and “sense”
the change of cellular mechanical phenotypes in a timely manner. Recently, it was
discovered that the soft substrates with physiological-relevant stiffness could
promote (or sometimes inhibit) a number of significant biological
transformations in stem cells or cancer cells. For example, Disher’s group found
that human mesenchymal stem cells could choose their lineage specification
according to the varied matrix elasticity [1]. Saif’s group discovered that the
human colon carcinoma (HCT-8) cells show a profound in vitro metastasis-like
phenotype when cultured on substrate with stiffness 20-40 kPa, but not on very
soft (1 kPa) and very stiff (3.6 GPa) substrates. It suggests that the onset of
in vivo cancer metastasis may, in part, be linked to the intracellular forces
and the mechanical microenvironment of the tumor [2]. Saif’s group also found
that cardiac cells could be mechanically coupled through the deformable
substrate, and that coupling decreases with increasing distance between them
and the substrate stiffness. The closer the cells are as a pair, higher is the
probability of both of them beating over longer time. The findings have
implications in the understanding of myocardial infarction when cardiac tissues
become stiff due to fibrotic scar formation [3].


Although all those biological transformations take a
certain period of days to accomplish, usually 7-10 days, people speculate that
there may exist a critical time-point, after which the cells suddenly and
irreversibly commit to the next state, whereas before which, cells remain
normal as usual. However, it is not exactly clear when this critical time-point
is. If, this time parameter can be determined, the understanding of cell
mechanosensitivity and the nature of the signaling networks underlying
biological tissues would be significantly enhanced.   


I believe AFM can surely help to shed new light on
solving this challenging problem, by monitoring the change of some essential
cellular mechanical phenotype, i.e. cell body and nuclear stiffness, cell
surface adhesion, cell membrane topography, and etc. It not only can provide valuable
cellular biophysical properties, but also avoids the artificial biological intervenes
resulted from the commonly adopted gene transfection approaches.



[1] A. Engler, S. Sen, H.L.
Sweeney, D.E. Discher. Matrix elasticity directs stem cell lineage
specification. Cell 126:677-689 (2006).

[2] Tang, X., T. B.
Kuhlenschmidt, M. S. Kuhlenschmidt, and M. T. A. Saif, "Mechanical Force
Affects Expression of an In vitro Metastasis-like Phenotype in HCT-8
cells," Biophysical Journal, Volume 99, Issue 8, 2460-2469, 20 October
2010. (Cover article)

[3] Tang, X., P. Bajaj, R.
Bashir, and M. T. A. Saif, "How Far Cardiac Cells Can See Each Other
Mechanically," Soft Matter (Cover article), 10.1039/C0SM01453B, 2011,
Advance Article.







Majid Minary's picture

Hi Xin,

Thanks for your comments, and suggesting new directions for application of AFM in cells mechanics. 

Thanks for posting the references. I had seen the second reference on the cover of Biophysical Journal.

I believe cell mechanics is truly one venue that AFM could have significant impact. Particularly coupling AFM With common optical/fluorescent microscopy could add to the information  obtained in many experiments. Could you also comment on how you measured the stiffness of the substrate in the above mentioned studies. I think AFM could be helpful in measuring mechanical properties of culture substrate with a high spatial resolution.

Fred Sansoz's picture

Dear Majid,

Thank you for presenting this interesting topic. Although my group is not working directly with biomaterials, we tried in the past to develop an AFM technique to improve the accuracy for force and hardness measurements on hard materials using AFM sapphire cantilevers mounted with cube-corner diamond tips, much like the geometry of tips in conventional instrumented nanoindenters. The reference to this study can be found here:

F. Sansoz and T. Gang, "A Force-Matching Method for Quantitative Hardness Measurements by Atomic Force Microscopy with Diamond-tipped Sapphire Cantilevers" , Ultramicroscopy, 111, 11-19 (2010)

This technique is general and has been tested on materials as hard as silicon and, more recently, on nanocrystalline Ni films like in the paper below, so it is more applicable to hard biological tissues.

F. Sansoz and K. D. Stevenson, "Relationship between Hardness and Dislocation Processes in a Nanocrystalline Metal at the Atomic Scale" , Physical Review B, 83, 224101 (2011).

Currently, we are working on extending this methodoloy to obtain more accurate hardness measurements in ultrathin nanowires and nanofibers by AFM nanoindentation, which is more challenging. If successful, this method should also find applications in the characterization of small, individual biological fibers like collagen fibrils. This is work in progress.

Majid Minary's picture

Hi Fred,

Thanks for interesting comments. Most often, new AFM methods start by application to more standard materials, before their transition to biological materials, due to extra challenge involved in soft tissues. Bone is one of the materials that could be used as transition to softer biological tissues. 

I had not come across sapphire cantilevers before. I know having diamond helps in maintaining the sharpness of the tip for extended period of time, which would help in obtaining much higher resolution images. 

Your second paper was intriguing for me, on subject that I may have forgotten to add. Combining computational methods such as large-scale MD with the information obtained from AFM experiments is a powerful and more complete approach to solve many complicated problems that cannot be address solely by either method. Keep us posted on the developments of your new work on nanowires and nanofibers. 


Xin Tang's picture

Dear Majid,

Yes, you raised a very good point. AFM is truly one of the ideal instruments to measure the mechanical stiffness of cell culture hydrogels. And to understand the mechanism of cell-substrate mechanical interaction, the precise measurement of substrate mechanical properties is essential.

I attached here 2 key references, introducing how to use the corrected Hertz model to extract hydrogel elastic modulus from AFM force-indentation curves. Also, in the supporting materials of my Biophysical Journal article, we have shown the fitted curves for the substrate of different elastic modulus. I hope it helps.

Engler, A. J., F. Rehfeldt, S. Sen, and D. E. Disher. 2007. Microtissue elasticity: measurements by Atomic Force Microscopy and its influence on cell differentiation. Methods in cell biology 83:521-545.

Dong, R., T. W. Jensen, K. Engberg, R. G. Nuzzo, and D. E. Leckband. 2007. Variably elastic hydrogel patterned via capillary action in microchannels. Langmuir 23: 1483-1488.

Martin Stolz's picture


Dear Majid,

Thank you for raising this important topic!

I have been working for quite some time in the field. For my Diploma thesis research I developed a Femtoampere-Pre-Amplifier, integrated it into a Scanning Tunneling Microscope (STM) and imaged organic thin films at molecular resolution. Next, I started a Ph.D. in Biology (- for me, the real interesting specimens are in the biomedical field).

My first poster on multiscale mechanical testing of cartilage using hard borosilicate glass spheres and sharp pyramidal indenters was presented at the American Society of Cell Biology (ASCB) in 1999 (Stolz et al., 1999). Since then my focus is on the mechanobiology of tissues and changes due to diseases. Over the last 15 years, I have co-developed a method, which we refer to as indentation-type AFM (IT-AFM), and which allows to early detect diseases in biological tissues. One of my key papers was published in the Biophysical Journal (Stolz et al., 2004). A refinement of this work was recently published in the Biophysical Journal (Loparic et al., 2010).

The atomic force microscope (AFM) provides the "eyes" and "fingers" to image, measure and manipulate soft biological matter. It allows to interact with complex biological systems such as molecular machines. The success of the AFM is documented by the numerous papers showing high resolved protein structures in their close-to-native environment. However, I believe that the highest potential of the AFM is in its diagnostic value. Remember that all physiological processes occur at the (sub-) cellular scale - and this is also the length scale where diseases start.

Current clinical tools are often limited in their diagnostic potential, because they only exhibit spatial resolutions at the tissue level. This limitation prevents an early diagnosis. IT-AFM provides a means of detecting the early signs of aging cartilage and osteoarthritis in mice and patient samples [cf. Stolz et al. (2009) Early detection of osteoarthritis and articular cartilage aging in mice and patient biopsies using atomic force microscopy. Nature Nanotechnology 4, 186-192]. ‘Faculty of 1000 Biology‘ evaluated this paper as "exceptional" and "a new concept and a real breakthrough".


The next obvious step is to move this from the bench into the clinic, by developing a user-friendly in situ IT-AFM setup for direct arthroscopic inspection. The arthroscopic AFM, targets the development of a new generation of diagnostic tools to provide hard numbers on the quality or ‘health' of tissues for an evidence-based medicine (Aigner et al., 2009; Imer et al., 2009). We are currently working on a new microfabricated sensor that is robust and reliable to implement IT-AFM into the arthroscopic AFM and enable similar analysis to that we regularly obtain on articular cartilage using a commercial AFM (Stolz et al., 2009). The arthroscopic AFM will fit into the trocar of a standard arthroscope to early detect osteoarthritis in the knee- or hip joints. To my personal believe, this clinical nanotool will be the prototype for a new generation of diagnostic tools.

There is the hope to develop magnetic resonance imaging (MRI) into a clinical tool for an early detection of osteoarthritis. The current in-plane resolution provided by MRI is of about 170 to 195 microns with a 0.5-1 mm slice thickness on a 7 T whole-body MR scanner inspecting the wrist (Chang et al., 2010). Therefore, MRI averages over more than 20 times larger volumes compared when using a 5 µm diameter spherical tip for IT-AFM microstiffness measurements (Stolz, 2011; Stolz et al., 2009). Given the current rate of technical developments it is highly speculative that MRI develops into a high resolution tool (Mansfield and Glover, 2002). I described my concerns for developing MRI into a tool for the early detection of osteoarthritis in a Letter to the Editor of the Journal of Biomechanics (Stolz et al., 2011). Since MRI cannot provide mechanical data, further analysis and quantification of the state of the disease and the amount of damage needs to be complemented by mechanical testing. Based on such larger scale data, the arthroscopic AFM may then enable a quantitative assessment of the degenerative stage of cartilage using the nanostiffness as a marker for matrix quality that is sensitive to normal functioning and that can detect cartilage degeneration. Therefore, the arthroscopic AFM is needed if MRI can be developed into a tool for the early detection of osteoarthritis, and there is also a need for such a clinical nanotool if MRI cannot serve this purpose.

I am happy to read and replay to your comments!

Best Wishes,




Aigner, T., N. Schmitz, and J. Haag. 2009. Nanomedicine: AFM tackles osteoarthritis. Nat Nanotechnol.4:144-145.

Chang, G., K.M. Friedrich, L. Wang, R.L.R. Vieira, M.E. Schweitzer, M.P. Recht, G.C. Wiggins, and R.R. Regatte. 2010. MRI of the wrist at 7 tesla using an eight-channel array coil combined with parallel imaging: preliminary results. J Magn Reson Imaging. 31:740-746.

Imer, R., T. Akiyama, F.d.R. N, M. Stolz, U. Aebi, F.F. N, and U. Staufer. 2009. The measurement of biomechanical properties of porcine articular cartilage using atomic force microscopy. Arch Histol Cytol. 72:251-259.

Loparic, M., D. Wirtz, A.U. Daniels, R. Raiteri, M.R. VanLandingham, G. Guex, I. Martin, U. Aebi, and M. Stolz. 2010. Micro- and Nanomechanical Analysis of Articular Cartilage by Indentation-Type Atomic Force Microscopy: Validation with a Gel-Microfiber Composite. Biophys J. 98:2731-2740.

Mansfield, P., and P.M. Glover. 2002. Limits to magnetic resonance microscopy. Rep. Prog. Phys. . 65:1489-1511.

Stolz, M., R. Gottardi, R. Raiteri, S. Miot, I. Martin, R. Imer, U. Staufer, A. Raducanu, M. Duggelin, W. Baschong, A.U. Daniels, N.F. Friederich, A. Aszodi, and U. Aebi. 2009. Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy. Nat Nanotechnol. 4:186-192.

Stolz, M., R. Raiteri, A.U. Daniels, M.R. VanLandingham, W. Baschong, and U. Aebi. 2004. Dynamic elastic modulus of porcine articular cartilage determined at two different levels of tissue organization by indentation-type atomic force microscopy. Biophys J. 86:3269-3283.

Stolz, M., J. Seidel, I. Martin, R. Raiteri, U. Aebi, and W. Baschong. 1999. Ex vivo measurement of the elasticity of extracellular matrix constituents by atomic force microscopy (AFM). Mol. Biol. Cell 10, 145a.


Majid Minary's picture

Hi Martin.

Thanks for posting this comprehensive note on the diagnostic applications of AFM, particularly on the early detection of osteoarthritis. Without a doubt, the resolution offered by AFM is superior to all available tools, particularly for biological applications. The area you are focused on is certainly promising for presenting AFM as a diagnostic tool in clinical applications.

One question I have is how easy it is to reach down to the cartilage in vivo using AFM and obtain the nano-mechanical measurement.




I gained a lot of knowledge after reading it! Thanks!

 I just want to know if you can somehow guide me regarding my advance studies?

I will be able to graduate as a mechanical engineer in December 2012...what options will I have in Ontario, Canada if I want to pursue some field related to biomechanics? Any small degree or course would do?

Or is it not meant for Engineers?


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