Reverse plasticity underlies rapid evolution by clonal selection within populations of fibroblasts propagated on a novel soft substrate

Mechanical properties such as substrate stiffness are a ubiquitous feature of a cell’s environment. Many types of animal cells exhibit canonical phenotypic plasticity when grown on substrates of differing stiffness, in vitro and in vivo. Whether such plasticity is a multivariate optimum due to hundreds of millions of years of animal evolution, or instead is a compromise between conflicting selective demands, is unknown. We addressed these questions by means of experimental evolution of populations of mouse fibroblasts propagated for approximately 90 cell generations on soft or stiff substrates. The ancestral cells grow twice as fast on stiff substrate as on soft substrate and exhibit the canonical phenotypic plasticity. Soft-selected lines derived from a genetically diverse ancestral population increased growth rate on soft substrate to the ancestral level on stiff substrate and evolved the same multivariate phenotype. The pattern of plasticity in the soft-selected lines was opposite of...

基底刚度（substrate stiffness）等机械特性是细胞微环境中普遍存在的特征。诸多动物细胞类型在体外（in vitro）和体内（in vivo）培养于不同刚度的基底时，均会表现出典型的表型可塑性（phenotypic plasticity）。目前尚不清楚这种表型可塑性究竟是经数亿年动物演化形成的多变量最优表型，还是相互冲突的选择压力共同作用下的折中结果。本研究通过对小鼠成纤维细胞（mouse fibroblasts）群体开展实验演化研究，使其在软基底或硬基底上传代约90个细胞世代，以此解答上述问题。祖先细胞在硬基底上的生长速率是软基底上的两倍，且表现出典型的表型可塑性。从遗传多样性的祖先群体中筛选得到的软基底适应细胞系，其在软基底上的生长速率提升至祖先细胞在硬基底上的水平，并演化出了相同的多变量表型。软基底适应细胞系的可塑性模式与……相反