Fig. 4. Synchronous application of strain magnitude and duty period promoted collagen production.

(A) Overview of the hypothesis test under the new condition for collagen and fibronectin production by MSCs. Left: The original pattern (R^hiε^loD^lo). Right: The new condition with dynamically synced STRAIN and DUTY, pattern (R^hiε^loD^lo sync). (B to E) Quantification of collagen and fibronectin production using metrics including (B) Col+ proportion, (C) collagen intensity, (D) weighted collagen, and (E) fibronectin intensity. N = 3 to 4 independent gels per condition. **P < 0.01 versus all other groups, *P < 0.05 versus ctrl and pattern (R^hiε^loD^lo), and #P < 0.1 versus pattern (R^hiε^hiD^hi). (F) Representative maximum intensity projections of cells stained with collagen and ED-A FN from tested conditions. Peripheral images are side view projections. (G) Schematic summarizing the interplay between STRAIN and DUTY, possibly manifested through integrative regulation of force loading rate via molecular clutch and imprinted mechanical memory, which ultimately control the mechano-responsiveness of MSCs. a.u., arbitrary units.