title: Effect of cell and microvillus mechanics on the transmission of applied loads to single bonds in dynamic force spectroscopy.
abstract: Receptor-ligand interactions that mediate cellular adhesion are often subjected to forces that regulate their detachment via modulating off-rates. Although the dynamics of detachment is primarily controlled by the physical chemistry of adhesion molecules, cellular features such as cell deformability and microvillus viscoelasticity have been shown to affect the rolling velocity of leukocytes in vitro through experiments and simulation. In this work, we demonstrate via various micromechanical models of two cells adhered by a single (intramolecular) bond that cell deformability and microvillus viscoelasticity modulate transmission of an applied external load to an intramolecular bond, and thus the dynamics of detachment. Specifically, it is demonstrated that the intermolecular bond force is not equivalent to the instantaneous applied force and that the instantaneous bond force decreases with cellular and microvillus compliance. As cellular compliance increases, not only does the time lag between the applied load and the bond force increase, an initial response time is observed during which cell deformation is observed without transfer of force to the bond. It is further demonstrated that following tether formation the instantaneous intramoleular bond force increases linearly at a rate dependent on microvillus viscosity. Monte Carlo simulations with fixed kinetic parameters predict that both cell and microvillus compliance increase the average rupture time, although the average rupture force based on bond length remains nearly unchanged.
authors.affiliation: University of Maryland Baltimore County, Baltimore, Maryland 21250, USA.
authors.forename: V K
authors.initials: VK
authors.lastname: Gupta
authors.forename: C D
authors.initials: CD
authors.lastname: Eggleton
mesh_terms: D001703:Biophysics / Q000379:methods*; D002448:Cell Adhesion / Q000502:physiology; D003198:Computer Simulation; D004548:Elasticity; D006801:Humans; D007700:Kinetics; D036904:Leukocyte Rolling / Q000502:physiology; D008024:Ligands; D008871:Microvilli / Q000378:metabolism*; D015233:Models, Statistical; D009010:Monte Carlo Method; D009504:Neutrophils / Q000166:cytology; D012984:Software; D013053:Spectrophotometry / Q000379:methods; D013314:Stress, Mechanical; D013997:Time Factors
chemical_list: D008024:Ligands