Dissecting the Impact of Matrix Anchorage and Elasticity in Cell Adhesion

Abstract

Extracellular matrices determine cellular fate decisions through the regulation of intracellular force and stress. Previous studies suggest that matrix stiffness and ligand anchorage cause distinct signaling effects. We show herein how defined noncovalent anchorage of adhesion ligands to elastic substrates allows for dissection of intracellular adhesion signaling pathways related to matrix stiffness and receptor forces. Quantitative analysis of the mechanical balance in cell adhesion using traction force microscopy revealed distinct scalings of the strain energy imparted by the cells on the substrates dependent either on matrix stiffness or on receptor force. Those scalings suggested the applicability of a linear elastic theoretical framework for the description of cell adhesion in a certain parameter range, which is cell-type-dependent. Besides the deconvolution of biophysical adhesion signaling, site-specific phosphorylation of focal adhesion kinase, dependent either on matrix stiffness or on receptor force, also demonstrated the dissection of biochemical signaling events in our approach. Moreover, the net contractile moment of the adherent cells and their strain energy exerted on the elastic substrate was found to be a robust measure of cell adhesion with a unifying power-law scaling exponent of 1.5 independent of matrix stiffness.

The Functional Response of Mesenchymal Stem Cells to Electron‐Beam Patterned Elastomeric Surfaces Presenting Micrometer to Nanoscale Heterogeneous Rigidity

“…[1] Increasingly, it is evident that matrix or tissue elasticity has a key role in regulating multiple cell processes, [2] including adhesion, [3] migration [4,5] and differential function [6,7] through cellgenerated actomyosin interactive forces regulated by cell-substrate adhesion and dynamic feedback mechanisms. [5] The sensitivity of cells to the mechanical properties of the extracellular matrix (ECM) is attributable to the mechanosensitive nature of the proteins associated with cell-ECM supramolecular adhesive complexes.…”

PlA2 Polymorphism in Glycoprotein IIb/IIIa Modulates the Morphology and Nanomechanics of Platelets

“…9,10 For a variety of cells, including stem cells, cancer cells, and inflammatory cells, it was shown that the cell membrane elasticity and the balance of biomechanical properties are vitally allied to the cell function and to cell differentiation, apoptosis, regeneration, specific cell activities, and so on. 11,12 Stiffness tomography investigations demonstrated changes in the actin cytoskeleton on actin depolymerization in fibroblasts.…”

Distinct impacts of substrate elasticity and ligand affinity on traction force evolution

“…[38][39][40] In contrast, other studies state that force magnitude depend linearly on adhesion area, while traction stress correlates with substrate stiffness. 13,20,21,45,46 In particular, viscous contributions, like friction at the cell-substrate interface, were hardly addressed up to now, although their impact on cellular traction forces was shown. 31,42 The force balance on cellular length scale and the state of the contractile actin cytoskeleton -and not the force balance at single adhesion sites -are considered as the regulating factors for force homeostasis of cells.…”

“…41 On the cell level there is an ongoing discussion how the overall cellular traction force is regulated in dependence on ECM parameters. 13 Two very recent works addressed the importance and options to investigate friction between the cell surface and the surrounding support. 21,34,41,43,44 However, the multitude of influencing parameters, including substrate viscoelasticity, ligand density and arrangement, cell type and their limited observation in a single experiment, led to various partly contradicting results and interpretations.…”