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  • Open Access

Endocytosis shapes extracellular chemical gradients in autonomous cell-cell attraction

Jeremy Barrios1, Andrew Goetz2, Susan E. Leggett3, and Purushottam D. Dixit2,4,5,6,*

  • *Contact author: purushottam.dixit@yale.edu
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Phys. Rev. Research 8, 033374 – Published 29 September, 2026

DOI: https://doi.org/10.1103/qn2h-7wml

Abstract

Receptor-mediated ligand endocytosis underlies essential homeostatic functions and in signaling contexts it is often regarded as a mechanism for signal attenuation. Here, we show that ligand removal can paradoxically enhance directional information in autonomous cell-cell attraction. Many cell systems migrate toward one another in the absence of externally imposed gradients, implying that secretion, diffusion, and uptake must themselves generate usable directional cues. We develop a surface-resolved theory of a finite-sized detector exposed to a nearby source and derive analytical expressions for the steady-state ligand field. The resulting concentration profiles are governed by a single dimensionless Damköhler number that compares receptor-mediated endocytosis to diffusive ligand transport. Increasing ligand removal lowers extracellular ligand concentrations and reduces absolute concentration differences across the detector surface, but preferentially enhances relative surface anisotropy. Thus, destroying the signal can increase the usable information encoded in relative gradients. Incorporating nonlinear downstream processing reveals a trade-off between contrast enhancement and signal depletion, with the directional response greatest within a joint regime of endocytosis and downstream sensing that overlaps the measured range of receptor internalization rates. These results recast receptor-mediated endocytosis as an extracellular information-processing mechanism that reshapes the surrounding ligand gradient to enhance directional information.

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Outline

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Phys. Rev. Research 8, 033374– Published 29 September, 2026
  • Received 20 April 2026
  • Accepted 27 July 2026
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Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

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