The distance between the plasma membrane and the actomyosin cortex acts as a nanogate to control cell surface mechanics

This article has been Reviewed by the following groups

Read the full article See related articles


Animal cell shape changes are controlled by the actomyosin cortex, a peripheral actin network tethered to the plasma membrane by membrane-to-cortex attachment (MCA) proteins. Previous studies have focused on how myosin motors or actin turnover can generate the local deformations required for morphogenesis. However, how the cell controls local actin nucleation remains poorly understood. By combining molecular engineering with biophysical approaches and in situ characterization of cortical actin network architecture, we show that membrane-to-cortex tethering determines the distance between the plasma membrane and the actomyosin cortex at the nanoscale of single actin nucleators. In turn, the size of this gap dictates actin filament production and the mechanical properties of the cell surface. Specifically, it tunes formin activity, controlling actin bundling and cortical tension. Our study defines the membrane-to-cortex distance as a nanogate that cells can open or close by MCA proteins to control the activity of key molecules at the cell surface.

Article activity feed

  1. This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at


    In this study, the authors did a fantastic job in deciphering a novel mechanism by which cortical tension can be regulated by increasing membrane-to-cortex tethering and discussed about a key parameter that controls the actomyosin cortical tension. The distance between the actomyosin cortex and the cell membrane connected by the membrane-to-cortex attachment (MCA) proteins dictates the cortical tension by regulating the production and bundling of actin filaments by nanogating formin entry and activity.

    The authors have thoroughly tested the possible role of different actin-associated proteins that regulate the cortical actomyosin architecture and cortical tension such as myosin, formins and Arp2/3 with proper controls. They did in depth analysis of the cortical actin architecture, its mean distance from the membrane and its effect on the overall cortical tension.

    This study unfolds a new dimension in understanding the architecture and mechanical properties of the cortical actomyosin network. However, here are few points, which really piqued my interest but were not self-explanatory to my understanding and can be critical to the overall understanding and conclusions of the research.

    Few Points:

    1.     The authors have tested the effect of CAezrin on the cortical tension and ruled out the possibility of the signaling component by testing the hypothesis using the iMC linker. However, they did not test the hypothesis with other MCA proteins such as radixin, moesin, etc., whether overexpression of these MCA proteins have similar effect as CAezrin. Testing the hypothesis with other MCAs would give insight into few perplexities the current study has including the following:

    a)     It is not clear whether the overexpression of a single type of MCA protein has an effect on the mean distance of actomyosin cortex from the membrane. Since the length of CAezrin (25 nm) is larger or almost comparable to the nanogating distance required for the formins to act (10-20 nm), it is not clear why formins were not gated to load on to the actin network with CAezrin overexpression. To have a more robust idea, the authors might be interested in testing other MCA proteins with different sizes leading to different mean distance between actomyosin cortex and the membrane affecting the cortical tension.

    b)     What is the effect of linkers with different affinity towards actin on the cortical tension? As we know based on the affinity of the actin linker proteins towards actin determine the temporal and spatial dynamics of actomyosin network. Testing MCA proteins with different actin affinity anchor protein would give us more insight about the architecture and tension of cortical actomyosin network.

    2.     The effect of Arp2/3 inhibition on the cortical tension in both +iMC and -iMC conditions was surprising considering the fact the inhibition of branching would result in overall loss of actin polymerization. Detailed study aiming at understanding the sequences of events that happen after Arp2/3 inhibition and the role of Arp2/3 in cortical tension regulation would help us understand this phenomenon better. In this regard, detailed study can be done to look at the effect of Arp2/3 inhibition on the F-actin turn over and their assembly into bundles, actin associated proteins that promote actin elongation and bundling and dissemble.

    3.     It is known from literature that formin-generated filaments represent less than 10% of all actin filaments. However, the effect on the nanogating is obviously drastic in terms of actomyosin cortex assembly and overall cortical tension. The authors might want to test the possible reason behind this phenomenon and test different possibilities. Is there a crosstalk between formin and other actin associated proteins thereby regulating the fate of actomyosin network and contractility?

    4.     The authors observed an increase in phosphorylated myosin-2 (p-myosin) at the cell periphery in the cells with overexpressed iMC-linkers. This is an interesting observation since with increase in p-myosin level, one would expect an increase in actomyosin contraction leading to higher cortical tension, which is opposite to what was observed in this condition. A detailed study about this phenomenon could potentially unfold a new insight into the understanding the actomyosin dynamics in the cell cortex. Could this be a compensatory feedback mechanism in response to loss of formin activity leading to loss of actin bundles?

    5.     The authors tested the possible involvement of mDia1 in regulating the actin bundling and overall cortical tension. However, detailed studies are needed to specifically infer how it can be regulated leading to changes in actin architecture and cortical tension.

    Competing interests

    The author declares that they have no competing interests.