Relationship of and cross-talk between physical and biologic properties of the glomerulus

Cells and tissues must respond to physical stresses. Cells exist in an elastic environment determined by their matrix, matrix contacts, cell-cell contacts, and cytoskeletal structure. We discuss the determinants of the elastic environment of cells and its potential roles in glomerular disease.

Control of the mechanical environment is sufficient to induce and maintain the differentiated state of cells including myofibroblasts. New experimental techniques permit precise measurement of the elastic characteristics of normal and diseased tissues and cells, and analysis of cell behavior and cytoskeletal structure in response to mechanical and elastic stimuli. Glomeruli become soft early in the course of several disease models, yet late stages are characterized by increased stiffness and fibrosis with loss of organ function. Work in hepatic fibrosis, arterial disease, and oncology demonstrate that increased collagen crosslinking by lysyl oxidase, an early step in the diseases, can result in a sufficient increase in tissue stiffness to alter cell behavior, leading to disease progression.

The elastic environment of cells and tissues provides essential signals in development, differentiation, and disease. Identifying the mechanisms that determine the mechanical environment of glomerular cells will complement other approaches to reduce pathologic fibrosis and loss of tissue function.