PENELOPE C. GEORGES
Dept. of Bioengineering, Institute for Medicine and Engineering, University of Pennsylvania, 3340 Smith Walk, Philadelphia, PA 19104, USA
ILYA LEVENTAL
Dept. of Bioengineering, Institute for Medicine and Engineering, University of Pennsylvania, 3340 Smith Walk, Philadelphia, PA 19104, USA
WILFREDO De JESúS ROJAS
Dept. of Bioengineering, Institute for Medicine and Engineering, University of Pennsylvania, 3340 Smith Walk, Philadelphia, PA 19104, USA
R. TYLER MILLER
Departments of Medicine and Physiology, Case Western Reserve University, Louis Stokes VAMC and Rammelkamp Center for Research, Cleveland, OH 44106, USA
PAUL A. JANMEY
Depts. of Physiology, Physics, and Bioengineering, Institute for Medicine and Engineering, University of Pennsylvania, 3340 Smith Walk, Philadelphia, PA 19104, USA

Received 21 September 2006
Revised 28 September 2006
Published

Most biological tissues are soft viscoelastic materials with elastic moduli ranging from approximately 100 to 100,000 Pa. Recent studies have examined the effect of substrate rigidity on cell structure and function, and many, but not all cell types exhibit a strong response to substrate stiffness. Some blood cells such as platelets and neutrophils have indistinguishable structures on hard and soft materials as long as they are sufficiently adhesive, whereas many cell types, including fibroblasts and endothelial cells spread much more strongly on rigid compared to soft substrates. A few cell types such as neurons appear to extend better on very soft materials. The different response of astrocytes and neurons to the stiffness of their substrate results in preferential growth of neurons on soft gels and astrocytes on hard gels, and suggests that preventing rigidification of damaged central nervous system tissue after injury may have utility in wound healing. How cells sense substrate stiffness is unknown. One candidate protein, filamin A, which responds to externally derived stresses, was tested in melanoma cells. Cells devoid of filamin A retain the ability to sense substrate stiffness, suggesting that other proteins are required for stiffness sensing.

Cytoskeleton; filamin; astrocyte; neuron