title: Cellular response to substrate rigidity is governed by either stress or strain.
abstract: Cells sense the rigidity of their substrate; however, little is known about the physical variables that determine their response to this rigidity. Here, we report traction stress measurements carried out using fibroblasts on polyacrylamide gels with Young's moduli ranging from 6 to 110 kPa. We prepared the substrates by employing a modified method that involves N-acryloyl-6-aminocaproic acid (ACA). ACA allows for covalent binding between proteins and elastomers and thus introduces a more stable immobilization of collagen onto the substrate when compared to the conventional method of using sulfo-succinimidyl-6-(4-azido-2-nitrophenyl-amino) hexanoate (sulfo-SANPAH). Cells remove extracellular matrix proteins off the surface of gels coated using sulfo-SANPAH, which corresponds to lower values of traction stress and substrate deformation compared to gels coated using ACA. On soft ACA gels (Young's modulus <20 kPa), cell-exerted substrate deformation remains constant, independent of the substrate Young's modulus. In contrast, on stiff substrates (Young's modulus >20 kPa), traction stress plateaus at a limiting value and the substrate deformation decreases with increasing substrate rigidity. Sustained substrate strain on soft substrates and sustained traction stress on stiff substrates suggest these may be factors governing cellular responses to substrate rigidity.
authors: Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
authors: Ai Kia
authors: AK
authors: Yip
authors: Katsuhiko
authors: K
authors: Iwasaki
authors: Chaitanya
authors: C
authors: Ursekar
authors: Hiroaki
authors: H
authors: Machiyama
authors: Mayur
authors: M
authors: Saxena
authors: Huiling
authors: H
authors: Chen
authors: Ichiro
authors: I
authors: Harada
authors: Keng-Hwee
authors: KH
authors: Chiam
authors: Yasuhiro
authors: Y
authors: Sawada
mesh_terms: D015119:Aminocaproic Acid / Q000494:pharmacology*; D000818:Animals; D001386:Azides / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D055119:Elastic Modulus / Q000187:drug effects; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism; D005782:Gels / Q000494:pharmacology; D051379:Mice; D041681:NIH 3T3 Cells; D013314:Stress, Mechanical; D013388:Succinimides / Q000494:pharmacology*
chemical_list: D001386:Azides; D005782:Gels; D013388:Succinimides; C062325:sulfosuccinimidyl 6-((4-azido-2-nitrophenyl)amino)hexanoate; D003094:Collagen; D015119:Aminocaproic Acid