Journal Club Theme of April 2009: Mechanobiology and Molecular Mechanomedicine
Professor YC Fung, the widely-recognized father of modern biomechanics, recently challenged the field by asking this fundamental question: “What axioms of the classical continuum mechanics have to be changed for biology?”
Our understanding of mechanobiology and biomechanics at the cellular and subcellular levels is rather primitive. For example, we do not know if a living cell differentiates a stress from a strain, or stress and strain are equivalent. In other words, we do not know whether living cells sense and respond to stress or strain. Nor do we understand by what mechanism a living cell respond to the rigidity of its substrate. It is clear that laws of physics are obeyed at the molecular levels (e.g., individual protein levels) as studies at molecular biophysics have shown (e.g., stretching a single talin protein, del Rio et al. Science, 2009; http://www.ncbi.nlm.nih.gov/pubmed/19179532). In this paper it is shown that in vitro a force of a physiologically relevant magnitude can unfold a talin to expose its cryptic binding site for vinculin, consistent with a paper published in 07 by D Discher’s group on forced unfolding of the spectrin molecule. However, it is not clear at all what classical continuum mechanics theories do not apply to biology at the cellular and subcellular levels and need to be changed.
Over the last decade, my colleagues and I focus on one aspect of this: stress propagation, distribution, and transduction in a living cell. We have found that stress propagation and transduction occur at a distance in a living cell, representing a major departure from the axiom of neighborhood (local action) of the classical continuum mechanics. See a recent perspective by N. Wang et al., published in Nature Reviews. In this paper it is explained how a localized stress at the cell surface can be channeled along cytoskeletal filaments and concentrated at distant sites in the cytoplasm and nucleus to induce mechanochemical conversion within the cytoplasm and possibly within the nucleus and alter gene activities.
One could also ask other fundamental questions about other axioms of continuum mechanics on their applicability to living cells and to the nucleus. For example, we basically know nothing about the role of mechanics in biology of epigenome (information that is carried in the genome and in the nucleus but not encoded in the DNA). While some view the living cell as a complex material, others view the living cell as a complex machine, but we should ask the question: how could these views/models help understand the unique “living” features of a cell? No matter what, the underlying governing rules or principles that dictate a living cell’s mechanical behaviors and biological functions remain largely elusive. For those who are interested in latest advances in mechanotransduction, please read a series of review papers at Nat Rev Mol Cell Biol in Jan 2009. For those who are interested in the future of biomechanics, it is suggested to read a perspective by some leading experts (D. Discher et al, Ann Biomed Eng. 2009 Mar 4. http://www.ncbi.nlm.nih.gov/pubmed/19259817).
Clearly time is ripe for mechanicians to work together with biologists, chemists, physicists, clinicians, and engineers, in order to make significant contributions to the field of mechanobiology. In the long term, for the field of mechanobiology and biomechanics to stand out as a striving field that benefits the general public, it should play a leading role in molecular mechanomedicine (application of mechanics/engineering based principles and technologies at molecular and cellular scales in vivo to the diagnosis, treatment, control, and cure of various human diseases).