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Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
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Image based modeling of bleb site selection.

Sharon Collier1, Peggy Paschke2, Robert R Kay2

  • 1MOAC Doctoral Training Centre, University of Warwick, Coventry, CV4 7AL, UK.

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|July 29, 2017
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Summary
This summary is machine-generated.

Cell geometry alone can predict where pressure-driven blebs form during cell migration. Adding a gradient in membrane-cortex adhesion improves predictions for more complex cell shapes and movement, highlighting physical forces in cell motility.

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Area of Science:

  • Cell Biology
  • Biophysics
  • Mechanobiology

Background:

  • Cells utilize rapid, pressure-driven blebs for movement and overcoming mechanical resistance.
  • The precise mechanisms governing bleb site selection and directionality to the cell front are not fully understood.
  • Previous research indicated Dictyostelium cells preferentially bleb from concave regions due to membrane tension facilitating detachment.

Purpose of the Study:

  • To develop a predictive model for bleb formation sites based on cell geometry.
  • To investigate the role of physical forces, specifically membrane tension and adhesion, in directing bleb formation.
  • To determine if cell geometry alone is sufficient to predict bleb locations.

Main Methods:

  • A novel computational modeling approach was employed, utilizing actual cell contours.
  • The model predicted bleb formation based on geometric parameters and physical forces.
  • Experimental validation involved observing bleb formation in migrating Dictyostelium cells.

Main Results:

  • Cell geometry alone successfully predicted bleb formation sites in rounded cells under high resistance.
  • The model's accuracy decreased with more polarized cells and lower resistance.
  • Incorporating a front-to-back gradient in membrane-cortex adhesion significantly improved model performance.
  • Talin, a protein linking membrane and cortex, was observed to form such a gradient.

Conclusions:

  • Physical forces, dictated by cell geometry, can be a primary determinant of bleb formation sites in certain cellular contexts.
  • A gradient in membrane-cortex adhesion, exemplified by Talin distribution, is crucial for accurate bleb site prediction in more complex migration scenarios.
  • The developed model offers a method to differentiate the contributions of physical forces versus other regulatory mechanisms in bleb formation.