Mechanobiology of bone marrow stem cells: from myosin-II forces to compliance of matrix and nucleus in cell forms and fates

Abstract

Adult stem cells and progenitors are of great interest for their clinical application as well as their potential to reveal deep sensitivities to microenvironmental factors. The bone marrow is a niche for at least two types of stem cells, and the prototype is the hematopoietic stem cell/progenitors (HSC/Ps), which have saved many thousands of patients for several decades now. In bone marrow, HSC/Ps interact functionally with marrow stromal cells that are often referred to as mesenchymal stem cells (MSCs) or derivatives thereof. Myosin and matrix elasticity greatly affect MSC function, and these mechanobiological factors are now being explored with HSC/Ps both in vitro and in vivo. Also emerging is a role for the nucleus as a mechanically sensitive organelle that is semi-permeable to transcription factors which are modified for nuclear entry by cytoplasmic mechanobiological pathways. Since therapies envisioned with induced pluripotent stem cells and embryonic stem cells generally involve in vitro commitment to an adult stem cell or progenitor, a very deep understanding of stem cell mechanobiology is essential to progress with these multi-potent cells.

Keywords: 3D; AFM; BM; BMT; Bleb; ECM; ESC; G-CSF; HSC/P; Hematopoiesis; MAL/MKL; MK; MLCK; MSC; Matrix; Mechanobiology; Myosin; NMM-II; Nucleus; OB; RBC; RLC; ROCK; SDF-1; SRF; YAP; atomic force microscopy; blebbistatin; bone marrow; bone marrow transplantation; embryonic stem cell; extracellular matrix; granulocyte colony-stimulating factor; hematopoietic stem cell/progenitor; kPa; kilopascal, units of elasticity; megakaryocyte; megakaryocytic acute leukemia protein; mesenchymal stem cell; myosin light chain kinase; non-muscle myosin-II; osteoblast; red blood cell; regulatory light chains; rho-associated protein kinase; serum response factor; stromal derived factor-1; three-dimensional; yes-associated protein.