Propagating Cell-Membrane Waves Driven by Curved Activators of Actin Polymerization

Cells exhibit propagating membrane waves which involve the actin cytoskeleton. One type of such membranal waves are Circular Dorsal Ruffles (CDR) which are related to endocytosis and receptor internalization. Experimentally, CDRs have been associated with membrane bound activators of actin polymerization of concave shape. We present experimental evidence for the localization of convex membrane proteins in these structures, and their insensitivity to inhibition of myosin II contractility in immortalized mouse embryo fibroblasts cell cultures. These observations lead us to propose a theoretical model which explains the formation of these waves due to the interplay between complexes that contain activators of actin polymerization and membrane-bound curved proteins of both types of curvature (concave and convex). Our model predicts that the activity of both types of curved proteins is essential for sustaining propagating waves, which are abolished when one type of curved activator is removed. Within this model waves are initiated when the level of actin polymerization induced by the curved activators is higher than some threshold value, which allows the cell to control CDR formation. We demonstrate that the model can explain many features of CDRs, and give several testable predictions. This work demonstrates the importance of curved membrane proteins in organizing the actin cytoskeleton and cell shape

Theoretical Model for Cellular Shapes Driven by Protrusive and Adhesive Forces

The forces that arise from the actin cytoskeleton play a crucial role in determining the cell shape. These include protrusive forces due to actin polymerization and adhesion to the external matrix. We present here a theoretical model for the cellular shapes resulting from the feedback between the membrane shape and the forces acting on the membrane, mediated by curvature-sensitive membrane complexes of a convex shape. In previous theoretical studies we have investigated the regimes of linear instability where spontaneous formation of cellular protrusions is initiated. Here we calculate the evolution of a two dimensional cell contour beyond the linear regime and determine the final steady-state shapes arising within the model. We find that shapes driven by adhesion or by actin polymerization (lamellipodia) have very different morphologies, as observed in cells. Furthermore, we find that as the strength of the protrusive forces diminish, the system approaches a stabilization of a periodic pattern of protrusions. This result can provide an explanation for a number of puzzling experimental observations regarding cellular shape dependence on the properties of the extra-cellular matrix

Curved inclusions surf membrane waves

In this letter we describe how membrane inclusions that have a spontaneous curvature, will be convected on the membrane due to the propagation of membrane waves. We calculate the Stokes drift of such particles and the effect on their overall density field. We solve analytically for a uniform sinusoidal wave in the absence of diffusion, and using simulations for the more realistic case of decaying waves with diffusion. In the latter case we provide some good analytic approximations. A variety of such membrane waves that propagate over a significant proportion of the cell surface exists in living cells, and we therefore show that they can play a role in transporting membrane proteins

Membrane-mediated interactions and the dynamics of dynamin oligomers on membrane tubes

Dynamin is a protein that plays a key role in the transport and recycling of membrane tubes and vesicles within a living cell. This protein adsorbs from solution to PIP2-containing membranes, and on these tubes it forms curved oligomers that condense into tight helical domains of uniform radius. The dynamics of this process is treated here in terms of the linear stability of a continuum model, whereby membrane-mediated interactions are shown to drive the spontaneous nucleation of condensed dynamin domains. We furthermore show that the deformation of the membrane outside the dynamin domains induces an energy barrier that can hinder the full coalescence of neighboring growing domains. We compare these calculations to experimental observations on dynamin dynamics in vitro

Cylindrical cellular geometry ensures fidelity of division site placement in fission yeast

10.1242/jcs.103788Journal of Cell Science125163850-3857JNCS

Avaliação da qualidade de vida em pacientes cirróticos com hérnia da parede abdominal Quality of life in patients with abdominal hernia and cirrhosis

RACIONAL: As hérnias de parede abdominal são um problema frequente no paciente cirrótico. Elas costumam ser volumosas e muito sintomáticas. OBJETIVO: Avaliar a qualidade de vida, através da aplicação do questionário Short Form-36 (SF-36), nos pacientes com hérnia e cirrose. MÉTODOS: Foram avaliados 39 pacientes cirróticos com hérnia de parede abdominal estratificados pela classificação de Child e submetidos ao questionário SF-36 por um mesmo profissional. RESULTADOS: A média dos escores obtidos no SF-36 mostra diminuição em todos os domínios nos pacientes cirróticos, principalmente no aspecto físico. O grupo Child B mostrou pior avaliação ao estado geral de saúde e capacidade funcional em relação ao grupo Child A, contudo não houve diferença em relação ao aspecto físico. CONCLUSÃO: A presença de hérnia de parede abdominal ocasiona piora na qualidade de vida do paciente cirrótico. A deterioração da função hepática está relacionada a pior qualidade de vida. A hérnia abdominal leva a restrição importante no aspecto físico também no Child A.<br>BACKGROUND: Abdominal hernias are frequent issue in cirrhotic patients. These hernias tend to be large and symptomatic. AIM: To analyze the quality of life using a Short Form-36 (SF-36) questionnaire in cirrhotic patients with abdominal hernia. METHODS: Thirty nine cirrhotic patients with abdominal wall hernia were analyzed. They were stratified according to Child´s classification and answered the SF-36 questionnaire administered by a same professional. RESULTS: The scores from SF-36 show impairment in all questionnaire domains in cirrhotic patients, especially in the physical aspect. The Child B group showed worse health general condition and functional capacity comparing with Child A group; however it did not show any significant difference related to physical aspect. CONCLUSION: The presence of abdominal hernia leads to worse quality of life in cirrhotic patients. Hepatic function deterioration is related to a worse quality of life. Abdominal hernia causes an important restriction in physical aspect even in Child A