Fig 2. Forces in stem cell trafficking.

(A) To extravasate from the circulation and invade a tissue, stem cells must adhere strongly to the vessel wall and withstand high flow forces. Within a tissue, additional physical factors can direct motile cells, including durotaxis into stiff, fibrotic regions of tissue where cells engraft. (B) Soft tissue elasticity scale ranging from soft brain (72), fat (73), and striated muscle (25), to stiff cartilage (E ~ 20–30 kPa at the scale of adhesions (74)) and pre-calcified bone (25). (C) In vitro substrates that mimic soft and stiff tissue microenvironments (left) show that cells anchor more strongly to stiff substrates, building focal adhesions and actin-myosin stress fibers. Schematic (right) shows matrix adhesion and growth factors influence both cell physiology and lineage. Signals from growth factor receptors not only propagate into the nucleus (dashed blue arrow) and direct transcription (black arrow), but also affect Rho-GTPase activity (dotted blue arrow). Rac drives motility forward, and Rho regulates contraction of stress fibers (red), and both can also influence gene expression (dotted red arrow).