Abstract

The shape and composition of a membrane directly regulate the localization, activity, and signaling properties of membrane associated proteins. Proteins that both sense and generate membrane curvature, e.g., through amphiphilic insertion motifs, potentially engage in recursive binding dynamics, where the recruitment of the protein itself changes the properties of the membrane substrate. Simple geometric models of membrane curvature interactions already provide prediction tools for experimental observations, however these models are treating curvature sensing and generation as separated phenomena. Here, we outline a model that applies both geometric and basic thermodynamic considerations. This model allows us to predict the consequences of recursive properties in such interaction schemes and thereby integrate the membrane as a dynamic substrate. We use this combined model to hypothesize the origin and properties of tubular carrier systems observed in cells. Furthermore, we pinpoint the coupling to a membrane reservoir as a factor that influences the membrane curvature sensing and generation properties of local curvatures in the cell in line with classic determinants such as lipid composition and membrane geometry.

Highlights

  • The cellular membrane is not merely an inert platform for cellular processes, but it actively regulates the localization, activity, and signaling properties of different types of proteins through geometric and/or compositional cues [1,2,3]

  • In addition to adsorptive binding regimes, selective recognition and stabilization of membrane geometries and compositions can be obtained through amphiphilic insertion motifs (AIMs), which geometries and compositions can be obtained through amphiphilic insertion motifs (AIMs), which are motifs that contain a hydrophilic part opposing a hydrophobic part [12,13]

  • Derivation of precise models for such pathways are beyond the scope of this review, we do consider it relevant to discuss the implementation of recursive MCS/membrane curvature generation (MCG)-changes, as these are already experienced in vitro, where curvature sensing AIMs promote fission and/or vesiculation of different membrane compartments [24,36,49]

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Summary

Introduction

The cellular membrane is not merely an inert platform for cellular processes, but it actively regulates the localization, activity, and signaling properties of different types of proteins through geometric and/or compositional cues [1,2,3]. Localization to specific lipid compositions can be mediated by interaction between protein domains, such as Phox (PX) and the Pleckstrin Homology (PH), and specific lipid headgroups [8], or via electrostatic interactions, e.g., Membranes 2017, 7, 6; doi:10.3390/membranes7010006 www.mdpi.com/journal/membranes. These domains domains show show high high specificity specificity for for certain membrane geometries that fit their inherent crescent shape [9,10,11].

Different
Two Insertion Regimes
Geometric
Geometric LPD-Model 1
Saturating
Geometric LPD-Model 2
Thermodynamic Insertion-Model
Basic Intrinsic Properties of Curved Membranes
Saturation of Insertion in Fixed Membrane Morphologies
Thermodynamic
Fission in a Closed Uncoupled Compartment
Fission
Recursive
Summary
Findings
Discussion
12. Effect
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