Diseased renal glomeruli are getting soft. Focus on “Biophysical properties of normal and diseased renal glomeruli”

tissues and cells are characterized by mechanical properties that are variously described as elasticity, deformability, or stiffness, which are critical components in determining their normal structure and function (reviewed in Ref. 25). However, biologists and physicians are not used to thinking of mechanical signals as having a primary role equivalent to biochemical signals in normal biology and disease. Appreciation of the importance of mechanical factors in biology, including the elastic properties of tissues and cells, has increased over the past 20 years. In many situations, mechanical factors, in collaboration with biochemical signals, have primary roles in the development and maintenance of tissue phenotype as well as disease. In this context, change from a soft (deformable ∼0.2 kPa) to a hard/dense (nondeformable >4 kPa) breast tissue represents a major risk factor for developing breast cancer, and females with higher levels of breast density are at higher risk for developing breast cancer (1). This is probably due to the fact that normal breast cells exposed to a stiff/hard extracellular environment (i.e., collagen-rich environment) lose their epithelial morphology as well as the ability to form acini and tend acquire a more invasive/malignant phenotype (18). Another example of how the elasticity of the surrounding environment determines cell behavior is offered by the liver. The elastic modulus of normal liver is ∼0.5 kPa but can increase to ∼15 kPa in the course of injury or fibrosis (6, 23). As a consequence of increased matrix stiffness, hepatocytes, stellate cells, and portal fibroblasts divide more rapidly, thus contributing to the disease (15). A third example is from studies showing that neurons grow selectively when brain cortical cells are plated on soft substrates (0.15–0.3 kPa) (7, 8). However, when the same cells are plated on more rigid substrate (2 kPa), glia grow selectively (7, 8). Thus it is clear that the mechanical properties of the extracellular environment are important contributors to cell lineage, cell proliferation, cell migration/invasion, and ultimately disease phenotypes.