Fibroblast Adaptation and Stiffness Matching to Soft Elastic Substrates

Abstract

Many cell types alter their morphology and gene expression profile when grown on chemically equivalent surfaces with different rigidities. One expectation of this change in morphology and composition is that the cell's internal stiffness, governed by cytoskeletal assembly and production of internal stresses, will change as a function of substrate stiffness. Atomic force microscopy was used to measure the stiffness of fibroblasts grown on fibronectin-coated polyacrylamide gels of shear moduli varying between 500 and 40,000 Pa. Indentation measurements show that the cells' elastic moduli were equal to, or slightly lower than, those of their substrates for a range of soft gels and reached a saturating value at a substrate rigidity of 20 kPa. The amount of cross-linked F-actin sedimenting at low centrifugal force also increased with substrate stiffness. Together with enhanced actin polymerization and cross-linking, active contraction of the cytoskeleton can also modulate stiffness by exploiting the nonlinear elasticity of semiflexible biopolymer networks. These results suggest that within a range of stiffness spanning that of soft tissues, fibroblasts tune their internal stiffness to match that of their substrate, and modulation of cellular stiffness by the rigidity of the environment may be a mechanism used to direct cell migration and wound repair.

Measuring Cell Viscoelastic Properties Using a Microfluidic Extensional Flow Device

“…For proof-of-principle studies, we focused on NIH 3T3 fibroblasts, which have been mechanically characterized by AFM (46,47), optical stretching (48,49), and MPA (50). To explore the potential of our cross-slot device for novel discovery, we also characterized GBM TICs, a stem-like subpopulation of GBM tumors thought to drive tumor initiation, recurrence, and therapeutic resistance (26,51,52).…”

Self-Assembled Peptide Amphiphile Nanofibers and PEG Composite Hydrogels as Tunable ECM Mimetic Microenvironment

“…15 Cells can sense the mechanical properties of their environment and as a response to perceived mechanical stimuli, they generate biochemical activity along with the signal transduction mechanism called mechanotransduction. 16,17 The matrix stiffness can regulate cellular functions including adhesion, 18 spreading, 19 migration, 20 proliferation, 21 and differentiation. 13,22 One of the most commonly used synthetic polymers to investigate the effects of mechanical stimuli on cellular behavior is poly(ethylene glycol) (PEG), which provides precise control of material stiffness.…”

Cellular contractility and substrate elasticity: a numerical investigation of the actin cytoskeleton and cell adhesion

“…The area covered by active integrins (shown in pink) is assumed to be small and therefore the area subjected to the non-specific tractions is assumed to be equal to the entire cell area. and Solon et al (2007). …”

“…Different ranges of substrate stiffness that influence cytoskeletal remodelling have been reported for different cell phenotypes; particularly, more contractile cells, such as myoblasts, are most sensitive up to ~400 kPa (Ren et al 2008), but less contractile cells, such as fibroblasts, are sensitive up to ~20 kPa (Yeung et al 2005). Previous in-vitro studies have quantified the effect of different substrate stiffness on stress fibre (SF) formation (Solon et al 2007), FA area (Goffin et al 2006), cell traction (Califano and Reinhart-King 2010), and cell shape (Yeung et al 2005). However, the cellular mechanisms underlying these phenomena are poorly understood.…”