Mechanobiology: A landscape for reinterpreting stem cell heterogeneity and regenerative potential in diseased tissues

Abstract

Mechanical forces play a fundamental role in cellular dynamics from the molecular level to the establishment of complex heterogeneity in somatic and stem cells. Here, we highlight the role of cytoskeletal mechanics and extracellular matrix in generating mechanical forces merging into oscillatory synchronized patterns. We discuss how cellular mechanosensing/-transduction can be modulated by mechanical forces to control tissue metabolism and set the basis for nonpharmacologic tissue rescue. Control of bone anabolic activity and repair, as well as obesity prevention, through a fine-tuning of the stem cell morphodynamics are highlighted. We also discuss the use of mechanical forces in the treatment of cardiovascular diseases and heart failure through the fine modulation of stem cell metabolic activity and regenerative potential. We finally focus on the new landscape of delivering specific mechanical stimuli to reprogram tissue-resident stem cells and enhance our self-healing potential, without the need for stem cell or tissue transplantation.

Keywords: Cell biology; Mechanobiology.

Graphical abstract

Figure 1

Cytoskeletal mechanics and (stem) cell heterogeneity Diagram showing a recap of the functions that involved tubulin and actin filaments depicted in the chapter.

Figure 2

The extracellular matrix, a relevant nanomechanical cue in framing stem cell heterogeneity Diagram focusing on the role of the continuous mechanical feedback sensing performed by the cell to compute and respond to the physical external stimuli leading, in the end, to morphogenetic reprogramming.