Signaling in the crowded cell

Ruth Nussinov*, Chung Jung Tsai, Hyunbum Jang

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations


High-resolution technologies have clarified some of the principles underlying cellular actions. However, understanding how cells receive, communicate, and respond to signals is still challenging. Questions include how efficient regulation of assemblies, which execute cell actions at the nanoscales, transmits productively at micrometer scales, especially considering the crowded environment, and how the cell organization makes it happen. Here, we describe how cells can navigate long-range diffusion-controlled signaling via association/dissociation of spatially proximal entities. Dynamic clusters can span the cell, engaging in most signaling steps. Effective local concentration, allostery, scaffolding, affinities, and the chemical and mechanical properties of the macromolecules and the environment play key roles. Signaling strength and duration matter, for example, deciding if a mutation promotes cancer or developmental syndromes.

Original languageEnglish
Pages (from-to)43-50
Number of pages8
JournalCurrent Opinion in Structural Biology
StatePublished - Dec 2021


FundersFunder number
U.S. Government
National Institutes of HealthHHSN26120080001E
U.S. Department of Health and Human Services
National Cancer Institute


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