Configurational entropy is an intrinsic driver of tissue structural heterogeneity.
Autor: | Srivastava V; Dept. of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USA., Hu JL; UC Berkeley-UC San Francisco Graduate Program in Bioengineering, Berkeley, CA 94720, USA., Garbe JC; Dept. of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USA.; Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA., Veytsman B; Chan Zuckerberg Initiative, Redwood City, CA 94963, USA.; School of Systems Biology, George Mason University, Fairfax, VA 22030, USA., Shalabi SF; Beckman Research Institute of City of Hope, Duarte, CA 91010, USA., Yllanes D; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.; Instituto de Biocomputaciòn y Fìsica de Sistemas Complejos (BIFI), 50018 Zaragoza, Spain., Thomson M; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., LaBarge MA; Beckman Research Institute of City of Hope, Duarte, CA 91010, USA., Huber G; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA., Gartner ZJ; Dept. of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USA.; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.; Center for Cellular Construction, University of California, San Francisco, CA 94158, USA. |
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Jazyk: | angličtina |
Zdroj: | BioRxiv : the preprint server for biology [bioRxiv] 2023 Jul 02. Date of Electronic Publication: 2023 Jul 02. |
DOI: | 10.1101/2023.07.01.546933 |
Abstrakt: | Tissues comprise ordered arrangements of cells that can be surprisingly disordered in their details. How the properties of single cells and their microenvironment contribute to the balance between order and disorder at the tissue-scale remains poorly understood. Here, we address this question using the self-organization of human mammary organoids as a model. We find that organoids behave like a dynamic structural ensemble at the steady state. We apply a maximum entropy formalism to derive the ensemble distribution from three measurable parameters - the degeneracy of structural states, interfacial energy, and tissue activity (the energy associated with positional fluctuations). We link these parameters with the molecular and microenvironmental factors that control them to precisely engineer the ensemble across multiple conditions. Our analysis reveals that the entropy associated with structural degeneracy sets a theoretical limit to tissue order and provides new insight for tissue engineering, development, and our understanding of disease progression. Competing Interests: DECLARATION OF INTERESTS Z.J.G. is an equity holder in Scribe biosciences, Provenance Bio, and Serotiny. |
Databáze: | MEDLINE |
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