title: Substrate compliance versus ligand density in cell on gel responses.
abstract: Substrate stiffness is emerging as an important physical factor in the response of many cell types. In agreement with findings on other anchorage-dependent cell lineages, aortic smooth muscle cells are found to spread and organize their cytoskeleton and focal adhesions much more so on "rigid" glass or "stiff" gels than on "soft" gels. Whereas these cells generally show maximal spreading on intermediate collagen densities, the limited spreading on soft gels is surprisingly insensitive to adhesive ligand density. Bell-shaped cell spreading curves encompassing all substrates are modeled by simple functions that couple ligand density to substrate stiffness. Although smooth muscle cells spread minimally on soft gels regardless of collagen, GFP-actin gives a slight overexpression of total actin that can override the soft gel response and drive spreading; GFP and GFP-paxillin do not have the same effect. The GFP-actin cells invariably show an organized filamentous cytoskeleton and clearly indicate that the cytoskeleton is at least one structural node in a signaling network that can override spreading limits typically dictated by soft gels. Based on such results, we hypothesize a central structural role for the cytoskeleton in driving the membrane outward during spreading whereas adhesion reinforces the spreading.
authors.affiliation: School of Engineering and Applied Science, Pennsylvania Muscle Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Engler
authors.forename: Lucie
authors.initials: L
authors.lastname: Bacakova
authors.forename: Cynthia
authors.initials: C
authors.lastname: Newman
authors.forename: Alina
authors.initials: A
authors.lastname: Hategan
authors.forename: Maureen
authors.initials: M
authors.lastname: Griffin
authors.forename: Dennis
authors.initials: D
authors.lastname: Discher
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D018929:Cell Culture Techniques / Q000379:methods; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D048429:Cell Size / Q000502:physiology; D003094:Collagen / Q000378:metabolism*; D003599:Cytoskeleton / Q000502:physiology* / Q000648:ultrastructure*; D004548:Elasticity; D005782:Gels; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000502:physiology*; D051381:Rats
chemical_list: D005782:Gels; D003094:Collagen