Cell size and shape affect cellular processes such as cell survival, growth and differentiation^1,2,3,4, thus establishing cell geometry as a fundamental regulator of cell physiology. The contributions of the cytoskeleton, specifically actomyosin tension, to these effects have been described, but the exact biophysical mechanisms that translate changes in cell geometry to changes in cell behaviour remain mostly unresolved. Using a variety of innovative materials techniques, we demonstrate that the nanostructure and lipid assembly within the cell plasma membrane are regulated by cell geometry in a ligand-independent manner. These biophysical changes trigger signalling events involving the serine/threonine kinase Akt/protein kinase B (PKB) that direct cell-geometry-dependent mesenchymal stem cell differentiation. Our study defines a central regulatory role by plasma membrane ordered lipid raft microdomains in modulating stem cell differentiation with potential translational applications.

细胞大小和形状会影响细胞过程，例如细胞存活、生长和分化^1,2,3,4，从而将细胞几何结构确立为细胞生理学的基本调节器。已经描述了细胞骨架，特别是肌动球蛋白张力对这些效应的贡献，但是将细胞几何形状的变化转化为细胞行为变化的确切生物物理机制仍然大部分未解决。使用多种创新材料技术，我们证明了细胞质膜内的纳米结构和脂质组装受细胞几何结构以独立于配体的方式调节。这些生物物理变化触发了涉及丝氨酸/苏氨酸激酶 Akt/蛋白激酶 B (PKB) 的信号事件，这些事件指导细胞几何依赖的间充质干细胞分化。