Fig. 1

Mesenchymal stem cells (MSCs) exhibit mechanical memory. a, b, c, d: MSCs differentiate into distinct lineages under different substrate stiffness conditions by upregulating lineage marker genes TUBB3 (<1 kPa stiffness, the neurogenic fate), PPARG (~1 kPa stiffness, the adipogenic fate), MYOD1 (~10 kPa stiffness, the myogenic fate), or RUNX2 (~40 kPa stiffness, the osteogenic fate). When re-seeded onto a soft substrate (~1 kPa), MSCs are expected to undergo adipogenic differentiation [1, 6, 64]. e, f: However, for higher first seeding stiffness values (>10 kPa), or for long first seeding durations (>10 days), mechanical memory leads to heterogeneous osteogenic differentiation [8]. g, h: The model predicts that for high first seeding stiffness values (~10 kPa), or for long first seeding durations, mechanical memory leads to heterogeneous myogenic differentiation