Entropic-elasticity-controlled dissociation and energetic-elasticity-controlled rupture induce catch to slip bonds in cell-adhes

In order to achieve a wide variety of biological phenomena, the abilities of cells to contact effectively and interact specifically with neighboring media play a central role. It is known that cells can sense the chemical and mechanical properties of surrounding systems and regulate their adhesion and movement through binding protein molecules within cell membrane. The kinetics of binding molecules interacting with ligands is of great interest in biophysical society. There are lots of discussions and contributions on cell mechanics from our mechanical society, e.g. Journal Club Theme of April 2007: Analytical Modeling of Biomolecules,  Cellular and Molecular Mechanics, cell mechanics summer school, cell and biomolecular mechanics in silico , and many others. The presentation by Prof. Cheng Zhu for the cell mechanics summer school is directly related to the work we show here.

The lifetime of biological bonds shortens exponentially with increasing tensile force, and such a bond behavior is usually termed as a ‘slip bond’ (Bell, 1 ). In the last few years, progresses in experimental techniques have enabled the mechanical activation of chemical bonds to be studied on both an individual basis and in a cluster composed of multiple bonds. Experiments have revealed that a small tensile force could strengthen bonds of adhesion molecules in the sense that bond lifetimes are prolonged. Such a binding behavior is termed as a ‘catch bond’, and was first predicted by Dembo et al. [2] . The prolonging of the lifetime of a bond cluster in response to tensile force was first observed by Thomas et al. [3] . The same trend was found on a single cell-adhesion molecule by Marshall et al. [4] . Studies by the latter revealed that bonds between P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) display a biphasic relationship between bond lifetime and applied force, whereby lifetime first increases and then decreases with increasing force.

We develop a physical model to describe the kinetic behavior in cell-adhesion molecules. Unbinding of non-covalent biological bonds is decomposed into bond dissociation and bond rupture. Such a treatment on debonding processes is a space decomposition of bond breaking events. Dissociation under thermal fluctuation is non-directional in a 3-dimensional space, and its energy barrier to escape may be not influenced by a tensile force but the microstates which can lead to dissociation are changed by the tensile force; rupture happens along the tensile force direction. An applied force effectively lowers the energy barrier to escape along the loading direction. The lifetime of the biological bond, due to the superimposition of two concurrent off-rates, may grow with increasing tensile force to moderate amount and decrease with further increasing load. We hypothesize that a catch-to-slip bond transition is a generic feature in biological bonds. The model also predicts that catch bonds in compliant molecular structure have longer lifetimes and may be activated at lower forces [5 , 6 , 7 ].

The paper is published in Phys. Rev. E, 77, 031910 (2008)
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