Adhesion to nanofibers drives cell membrane remodeling through one-dimensional wetting

Arthur Charles-Orszag,Françoise Brochard-Wyart,Aurélie Bertin,Sylvie Goussard,Martin Sachse,Feng-Ching Tsai,Patricia Bassereau,Pierre Lafaye,Valeria Manriquez,Keira Melican,Corinne Millien,Adeline Mallet,Audrey Salles,Matthieu Piel,Jacomine Krijnse-Locker,Guillaume Duménil,Ralitza Staneva,Spencer Shorte,Daria Bonazzi

doi:10.1038/s41467-018-06948-x

Abstract

The shape of cellular membranes is highly regulated by a set of conserved mechanisms that can be manipulated by bacterial pathogens to infect cells. Remodeling of the plasma membrane of endothelial cells by the bacterium Neisseria meningitidis is thought to be essential during the blood phase of meningococcal infection, but the underlying mechanisms are unclear. Here we show that plasma membrane remodeling occurs independently of F-actin, along meningococcal type IV pili fibers, by a physical mechanism that we term ‘one-dimensional’ membrane wetting. We provide a theoretical model that describes the physical basis of one-dimensional wetting and show that this mechanism occurs in model membranes interacting with nanofibers, and in human cells interacting with extracellular matrix meshworks. We propose one-dimensional wetting as a new general principle driving the interaction of cells with their environment at the nanoscale that is diverted by meningococci during infection.

Highlights

The shape of cellular membranes is highly regulated by a set of conserved mechanisms that can be manipulated by bacterial pathogens to infect cells
Staining of human blood vessels during vascular colonization by N. meningitidis revealed that the surface of human endothelial cells was reorganized in the form of plasma membrane protrusions that intercalated between aggregated bacteria (Fig. 1a and Supplementary Figure 1a and b), co-localized with T4P (Fig. 1a), and were enriched in F-actin (Supplementary Figure 1a), paralleling earlier in vitro studies[11,16,17]
When cultured on such matrices, human endothelial cells showed nanoscale plasma membrane protrusions that aligned onto fibers of 5 to about 30 nm (Fig. 4g). This set of experiments shows that cell membranes can form protrusions when adhering on naturally occurring nanofibers such as those found in the ECM. Taken together, these data show that adhesive nanofibers can drive the remodeling of biological membranes at the nanoscale because of a wetting phenomenon that falls into a new regime that we named “1D” membrane wetting

Summary

Introduction

The shape of cellular membranes is highly regulated by a set of conserved mechanisms that can be manipulated by bacterial pathogens to infect cells. In the context of pathological conditions, especially in bacterial, viral and fungal infections, pathogens manipulate the shape of the plasma membrane to enter host cells. This is often achieved by diverting the actin cytoskeleton[6,7,8]. We show that the ability of nanoscale fibers to drive membrane remodeling is true for other naturally occurring fibers such as the ones found in native extracellular matrices, suggesting that one-dimensional membrane wetting is a general mechanism for plasma membrane remodeling in human cells

Methods

Results

Conclusion