Fig. 6.

Schematic illustration of the concept of mechanical stress magnitude (MSM) thresholds for cell proliferation and differentiation pattern formation. (A) Two MSM thresholds are proposed: a lower MSM threshold (T_l), below which cell aggregates do not respond by formation of cell and differentiation patterns (zone I), and an upper MSM threshold (T_u), above which cell aggregates do not further alter their proliferation and differentiation patterns (zone III). The range from T_l and T_u forms a MSM window (termed “window stress threshold”) within which mechanical stresses dictate the formation of cell proliferation and differentiation patterns (zone II). (B) An example of cell aggregate response. Zones I and II correspond to the inner region and perimeter of the triangular cell island, respectively, while zone III spans across the entire island when mechanical stresses are elevated above T_u such as by application of 8% mechanical stretching.