Effect of viscoelasticity on the analysis of single-molecule force spectroscopy on live cells.

Abstract:

:Single-molecule force spectroscopy is used to probe the kinetics of receptor-ligand bonds by applying mechanical forces to an intermediate media on which the molecules reside. When this intermediate media is a live cell, the viscoelastic properties can affect the calculation of rate constants. We theoretically investigate the effect of media viscoelasticity on the common assumption that the bond force is equal to the instantaneous applied force. Dynamic force spectroscopy is simulated between two cells of varying micromechanical properties adhered by a single bond with a constant kinetic off-rate. We show that cell and microvilli deformation, and hydrodynamic drag contribute to bond forces that can be 28-90% lower than the applied force for loading rates of 10(3)-10(7) pN/s, resulting in longer bond lifetimes. These longer bond lifetimes are not caused by changes in bond kinetics; rather, they are due to the mechanical response of the intermediate media on which the bonds reside. Under the assumption that the instantaneous bond force is equal to the applied force--thereby ignoring viscoelasticity--leads to 14-39% error in the determination of off-rates. We present an approach that incorporates viscoelastic properties in calculating the instantaneous bond force and kinetic dissociation parameter of the intermolecular bond.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Gupta VK,Neeves KB,Eggleton CD

doi

10.1016/j.bpj.2012.05.044

subject

Has Abstract

pub_date

2012-07-03 00:00:00

pages

137-45

issue

1

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(12)00624-8

journal_volume

103

pub_type

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