skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


This content will become publicly available on March 17, 2026

Title: Phase-field Approach to Cellular Blebbing
Bulges in the plasma membrane of cells known as blebs can form spontaneously in a wide range of biological processes but what controls their shape and stability remains incompletely understood. To address this, we introduce a dual phase-field model with coupled order parameters representing the cell cortex and plasma membrane that can quantitatively model blebbing in three dimensions. Simulations and analysis of the model reveal that, depending on whether blebbing occurs by detachment of the plasma membrane or rupture of the actin cortex, blebs can form discontinuously through a saddle node bifurcation or continuously with increasing cortical tension. The model predictions are in good quantitative agreement with existing experimental data for laser-induced cortex rupture.  more » « less
Award ID(s):
2019745
PAR ID:
10597041
Author(s) / Creator(s):
; ;
Publisher / Repository:
bioRxiv
Date Published:
Format(s):
Medium: X
Institution:
bioRxiv
Sponsoring Org:
National Science Foundation
More Like this
  1. Cell migration is critical for many vital processes, such as wound healing, as well as harmful processes, such as cancer metastasis. Experiments have highlighted the diversity in migration strategies employed by cells in physiologically relevant environments. In 3D fibrous matrices and confinement between two surfaces, some cells migrate using round membrane protrusions, called blebs. In bleb-based migration, the role of substrate adhesion is thought to be minimal, and it remains unclear if a cell can migrate without any adhesion complexes. We present a 2D computational fluid-structure model of a cell using cycles of bleb expansion and retraction in a channel with several geometries. The cell model consists of a plasma membrane, an underlying actin cortex, and viscous cytoplasm. Cellular structures are immersed in viscous fluid which permeates them, and the fluid equations are solved using the method of regularized Stokeslets. Simulations show that the cell cannot effectively migrate when the actin cortex is modeled as a purely elastic material. We find that cells do migrate in rigid channels if actin turnover is included with a viscoelastic description for the cortex. Our study highlights the non-trivial relationship between cell rheology and its external environment during migration with cytoplasmic streaming. 
    more » « less
  2. Abstract The accumulation and transmission of mechanical stresses in the cell cortex and membrane determines the mechanics of cell shape and coordinates essential physical behaviors, from cell polarization to cell migration. However, the extent that the membrane and cytoskeleton each contribute to the transmission of mechanical stresses to coordinate diverse behaviors is unclear. Here, we reconstitute a minimal model of the actomyosin cortex within liposomes that adheres, spreads and ultimately ruptures on a surface. During spreading, accumulated adhesion-induced (passive) stresses within the membrane drive changes in the spatial assembly of actin. By contrast, during rupture, accumulated myosin-induced (active) stresses within the cortex determine the rate of pore opening. Thus, in the same system, devoid of biochemical regulation, the membrane and cortex can each play a passive or active role in the generation and transmission of mechanical stress, and their relative roles drive diverse biomimetic physical behaviors. 
    more » « less
  3. Several groups have recently reported evidence for the emergence of domains in cell plasma membranes when membrane proteins are organized by ligand binding or assembly of membrane proximal scaffolds. These domains recruit and retain components that favor the liquid-ordered phase, adding to a decades-old literature interrogating the contribution of membrane phase separation in plasma membrane organization and function. Here we propose that both past and present observations are consistent with a model in which membranes have a high compositional susceptibility, arising from their thermodynamic state in a single phase that is close to a miscibility phase transition. This rigorous framework naturally allows for both transient structure in the form of composition fluctuations and long-lived structure in the form of induced domains. In this way, the biological tuning of plasma membrane composition enables a responsive compositional landscape that facilitates and augments cellular biochemistry vital to plasma membrane functions. 
    more » « less
  4. Abstract Necroptosis is a form of inflammatory lytic cell death involving active cytokine production and plasma membrane rupture. Progression of necroptosis is tightly regulated in time and space, and its signaling outcomes can shape the local inflammatory environment of cells and tissues. Pharmacological induction of necroptosis is well established, but the diffusive nature of chemical death inducers makes it challenging to study cell‐cell communication precisely during necroptosis. Receptor‐interacting protein kinase 3, or RIPK3, is a crucial signaling component of necroptosis, acting as a crucial signaling node for both canonical and non‐canonical necroptosis. RIPK3 oligomerization is crucial to the formation of the necrosome, which regulates plasma membrane rupture and cytokine production. Commonly used necroptosis inducers can activate multiple downstream signaling pathways, confounding the signaling outcomes of RIPK3‐mediated necroptosis. Opsin‐free optogenetic techniques may provide an alternative strategy to address this issue. Optogenetics uses light‐sensitive protein‐protein interaction to modulate cell signaling. Compared to chemical‐based approaches, optogenetic strategies allow for spatiotemporal modulation of signal transduction in live cells and animals. We developed an optogenetic system that allows for ligand‐free optical control of RIPK3 oligomerization and necroptosis. This article describes the sample preparation, experimental setup, and optimization required to achieve robust optogenetic induction of RIPK3‐mediated necroptosis in colorectal HT‐29 cells. We expect that this optogenetic system could provide valuable insights into the dynamic nature of lytic cell death. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Production of lentivirus encoding the optogenetic RIPK3 system Support Protocol: Quantification of the titer of lentivirus Basic Protocol 2: Culturing, chemical transfection, and lentivirus transduction of HT‐29 cells Basic Protocol 3: Optimization of optogenetic stimulation conditions Basic Protocol 4: Time‐stamped live‐cell imaging of HT‐29 lytic cell death Basic Protocol 5: Quantification of HT‐29 lytic cell death 
    more » « less
  5. null (Ed.)
    Abstract This paper focuses on the derivation and simulation of mathematical models describing new plasma fraction in blood for patients undergoing simultaneous extracorporeal membrane oxygenation and therapeutic plasma exchange. Models for plasma exchange with either veno-arterial or veno-venous extracorporeal membrane oxygenation are considered. Two classes of models are derived for each case, one in the form of an algebraic delay equation and another in the form of a system of delay differential equations. In special cases, our models reduce to single compartment ones for plasma exchange that have been validated with experimental data (Randerson et al., 1982, Artif. Organs, 6, 43–49). We also show that the algebraic differential equations are forward Euler discretizations of the delay differential equations, with timesteps equal to transit times through model compartments. Numerical simulations are performed to compare different model types, to investigate the impact of plasma device port switching on the efficiency of the exchange process, and to study the sensitivity of the models to their parameters. 
    more » « less