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Cell Syst ; 9(5): 496-507.e5, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31606369

RESUMO

Although F-actin has a large number of binding partners and regulators, the number of phenotypic states available to the actin cytoskeleton is unknown. Here, we quantified 74 features defining filamentous actin (F-actin) and cellular morphology in >25 million cells after treatment with a library of 114,400 structurally diverse compounds. After reducing the dimensionality of these data, only ∼25 recurrent F-actin phenotypes emerged, each defined by distinct quantitative features that could be machine learned. We identified 2,003 unknown compounds as inducers of actin-related phenotypes, including two that directly bind the focal adhesion protein, talin. Moreover, we observed that compounds with distinct molecular mechanisms could induce equivalent phenotypes and that initially divergent cellular responses could converge over time. These findings suggest a conceptual parallel between the actin cytoskeleton and gene regulatory networks, where the theoretical plasticity of interactions is nearly infinite, yet phenotypes in vivo are constrained into a limited subset of practicable configurations.


Assuntos
Citoesqueleto de Actina/química , Actinas/química , Adaptação Fisiológica/fisiologia , Citoesqueleto de Actina/fisiologia , Actinas/metabolismo , Sequência de Aminoácidos , Adesão Celular/fisiologia , Linhagem Celular Tumoral , Citoesqueleto/metabolismo , Feminino , Ensaios de Triagem em Larga Escala/métodos , Humanos , Ligação Proteica , Talina/metabolismo
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