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Probing Cellular Mechanoadaptation Using Cell-Substrate De-Adhesion Dynamics: Experiments and Model

DSpace at IIT Bombay

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Title Probing Cellular Mechanoadaptation Using Cell-Substrate De-Adhesion Dynamics: Experiments and Model
 
Creator SOUMYA, SS
STHANAM, LK
PADINHATEERI, R
INAMDAR, MM
SEN, S
 
Subject MATRIX-RIGIDITY
FOCAL ADHESIONS
LIGAND DENSITY
ADHERENT CELLS
ELASTICITY
STIFFNESS
CONTRACTILITY
MECHANICS
MOTILITY
POLARIZATION
 
Description Physical properties of the extracellular matrix (ECM) are known to regulate cellular processes ranging from spreading to differentiation, with alterations in cell phenotype closely associated with changes in physical properties of cells themselves. When plated on substrates of varying stiffness, fibroblasts have been shown to exhibit stiffness matching property, wherein cell cortical stiffness increases in proportion to substrate stiffness up to 5 kPa, and subsequently saturates. Similar mechanoadaptation responses have also been observed in other cell types. Trypsin de-adhesion represents a simple experimental framework for probing the contractile mechanics of adherent cells, with de-adhesion timescales shown to scale inversely with cortical stiffness values. In this study, we combine experiments and computation in deciphering the influence of substrate properties in regulating de-adhesion dynamics of adherent cells. We first show that NIH 3T3 fibroblasts cultured on collagen-coated polyacrylamide hydrogels de-adhere faster on stiffer substrates. Using a simple computational model, we qualitatively show how substrate stiffness and cell-substrate bond breakage rate collectively influence de-adhesion timescales, and also obtain analytical expressions of de-adhesion timescales in certain regimes of the parameter space. Finally, by comparing stiffness-dependent experimental and computational de-adhesion responses, we show that faster de-adhesion on stiffer substrates arises due to force-dependent breakage of cell-matrix adhesions. In addition to illustrating the utility of employing trypsin de-adhesion as a biophysical tool for probing mechanoadaptation, our computational results highlight the collective interplay of substrate properties and bond breakage rate in setting de-adhesion timescales.
 
Publisher PUBLIC LIBRARY SCIENCE
 
Date 2014-12-29T06:32:35Z
2014-12-29T06:32:35Z
2014
 
Type Article
 
Identifier PLOS ONE, 9(9)
1932-6203
http://dx.doi.org/10.1371/journal.pone.0106915
http://dspace.library.iitb.ac.in/jspui/handle/100/17318
 
Language English