Fig. 2
Hematopoietic stem cells (HSCs) are stimulated by the biochemical, biological, and physical parameters of the microenvironment in vivo. HSCs are subjected to biochemical and biological signals elicited by cell–cell interactions including direct contacts and communication through soluble factors as well as cell–matrix interactions. At the same time, cells are stimulated by the physical parameters of the environment. Intrinsic forces (Fi) are generated intracellularly and transferred to other cells through cell–cell junctions, such as cadherin receptors, or via traction on extracellular matrix (ECM) adhesion ligands those are bound to integrin receptors. Extrinsic forces (Fe) are externally applied by shear or tension and/or compression on cells, and they can be sensed by mechanically gated ion channels, changes in receptor-ligand binding, deformation of the cytoskeleton, and the primary cilium. Physical properties, for example, the elastic modulus and nanotopography of the ECM, govern how mechanical cues are transduced. The cytoskeleton generates and transfers forces from membrane proteins to intracellular structures, such as the nucleus