A phosphoinositide-based model of actin waves in frustrated phagocytosis

Marco A. Avila Ponce de León, Bryan Félix, Hans G. Othmer

Research output: Contribution to journalArticlepeer-review

Abstract

Phagocytosis is a complex process by which phagocytes such as lymphocytes or macrophages engulf and destroy foreign bodies called pathogens in a tissue. The process is triggered by the detection of antibodies that trigger signaling mechanisms that control the changes of the cellular cytoskeleton needed for engulfment of the pathogen. A mathematical model of the entire process would be extremely complicated, because the signaling and cytoskeletal changes produce large mechanical deformations of the cell. Recent experiments have used a confinement technique that leads to a process called frustrated phagocytosis, in which the membrane does not deform, but rather, signaling triggers actin waves that propagate along the boundary of the cell. This eliminates the large-scale deformations and facilitates modeling of the wave dynamics. Herein we develop a model of the actin dynamics observed in frustrated phagocytosis and show that it can replicate the experimental observations. We identify the key components that control the actin waves and make a number of experimentally-testable predictions. In particular, we predict that diffusion coefficients of membrane-bound species must be larger behind the wavefront to replicate the internal structure of the waves. Our model is a first step toward a more complete model of phagocytosis, and provides insights into circular dorsal ruffles as well.

Original languageEnglish (US)
Article number110764
JournalJournal of Theoretical Biology
Volume527
DOIs
StatePublished - Oct 21 2021

Bibliographical note

Funding Information:
Supported in part by NIH Grant # GM29123, NSF award CON-75851, project 00074041, and NSF Grant DMS # 1311974 and 1853357. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2021 Elsevier Ltd

Keywords

  • Actin waves
  • Mathematical model
  • Phagocytosis
  • Phosphoinositides

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

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