Cell Movement Is Guided by the Rigidity of the Substrate

Abstract

Directional cell locomotion is critical in many physiological processes, including morphogenesis, the immune response, and wound healing. It is well known that in these processes cell movements can be guided by gradients of various chemical signals. In this study, we demonstrate that cell movement can also be guided by purely physical interactions at the cell-substrate interface. We cultured National Institutes of Health 3T3 fibroblasts on flexible polyacrylamide sheets coated with type I collagen. A transition in rigidity was introduced in the central region of the sheet by a discontinuity in the concentration of the bis-acrylamide cross-linker. Cells approaching the transition region from the soft side could easily migrate across the boundary, with a concurrent increase in spreading area and traction forces. In contrast, cells migrating from the stiff side turned around or retracted as they reached the boundary. We call this apparent preference for a stiff substrate "durotaxis." In addition to substrate rigidity, we discovered that cell movement could also be guided by manipulating the flexible substrate to produce mechanical strains in the front or rear of a polarized cell. We conclude that changes in tissue rigidity and strain could play an important controlling role in a number of normal and pathological processes involving cell locomotion.

Surface Curvature Differentially Regulates Stem Cell Migration and Differentiation via Altered Attachment Morphology and Nuclear Deformation

“…In regeneration, human mesenchymal stem cells (hMSCs) from the bone marrow stroma are believed to play an important role due to their ability for self‐renewal and differentiation into different mature cells like osteoblasts, adipocytes and chondrocytes 5. Numerous studies have shown that the mechanical properties of the cell's microenvironment, such as the substrate stiffness, have a fundamental effect on hMSC cell fate and function and impact tissue regeneration 6, 7, 8, 9. Recently, evidence is rising that the geometrical properties of the cell's environment also play an important role as regulators of cell behavior 10, 11, 12, 13, 14, 15, 16, 17, 18, 19.…”

Numerical modeling of cell differentiation and proliferation in force-induced substrates via encapsulated magnetic nanoparticles

“…This mutually dependent relationship between cells and their surrounding matrices is often referred to as dynamic reciprocity [13]. Consequently, besides other cell reactions [38,39,41], cells may respond to changes in their mechanical environment, such as changes in matrix rigidity, by undergoing differentiation and/or proliferation [13,43]. For instance, experiments have demonstrated that for soft matrices that resembling brain tissue (0.1-1 kPa) SCs differentiate to neurogenic cells, for intermediate matrices that mimicking cartilage tissue (20-25 kPa) they differentiate into chondrogenic cells, and comparatively hard matrices that mimic the tissue of collagenous bone (30-45 kPa) they differentiate into osteogenic cells [13,26,40,55].…”

A theoretical model for fibroblast-controlled growth of saccular cerebral aneurysms

“…The fibroblast belongs to the group of adherent cells, and attaches to the ECM by integrins (Cukierman et al, 2001;Jiang and Grinnell, 2005). The mobility of the fibroblast and its ability to contract the ECM are important properties in the maintenance of the ECM (Barocas et al, 1995;Dembo and Wang, 1999;Eastwood et al, 1998;Friedl and Bröcker, 2000;Friedrichs et al, 2007;Grinnell, 2003;Lo et al, 2000;Poole et al, 2005). The fibroblast also has the ability to align itself in the direction of existing collagen fibres and to produce new collagen that is aligned in the same direction (Birk et al, 1990;Cisneros et al, 2006;Friedrichs et al, 2007;Huang et al, 1993;Lin et al, 1999;Meshel et al, 2005;Tóth et al, 1998).…”