Protein induced lipid demixing in homogeneous membranes

Letter
Open Access

Protein induced lipid demixing in homogeneous membranes

Bernd Henning Stumpf, Piotr Nowakowski, Christian Eggeling, Anna Maciołek, and Ana-Sunčana Smith

Phys. Rev. Research 3, L042013 – Published 29 October 2021

Abstract

Specific lipid environments are necessary for the establishment of protein signaling platforms in membranes, yet their origin has been highly debated. We present a continuum, exactly solvable model of protein induced local demixing of lipid membranes. The coupling between a local composition and a local thickness of the membrane induces lipid domains around inclusions with hydrophobic mismatch, even for temperatures above the miscibility critical point of the membrane. The model qualitatively explains the experimentally observed formation of lipid domains induced by anchoring of reconstituted actin in flat supported lipid bilayers.

Received 31 May 2021
Accepted 14 September 2021

DOI:https://doi.org/10.1103/PhysRevResearch.3.L042013

Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

Published by the American Physical Society

Physics Subject Headings (PhySH)

Phase separation Protein-membrane interactions Protein-protein interactions Structural order parameter

Landau-Ginzburg theory Path-integral methods

Physics of Living SystemsStatistical Physics & ThermodynamicsCondensed Matter, Materials & Applied Physics

Authors & Affiliations

Bernd Henning Stumpf ¹, Piotr Nowakowski ^2,3, Christian Eggeling ^4,5,6, Anna Maciołek ^2,7, and Ana-Sunčana Smith ^1,8,*

¹PULS Group, Institut für Theoretische Physik, IZNF, Friedrich-Alexander-Universität Erlangen-Nürnberg, Cauerstraße 3, 91058 Erlangen, Germany
²Max-Planck-Institut für Intelligente Systeme Stuttgart, Heisenbergstrasse 3, 70569 Stuttgart, Germany
³Institut für Theoretische Physik IV, Universität Stuttgart, Pfaffenwaldring 57, 70569 Stuttgart, Germany
⁴Institute of Applied Optics and Biophysics, Friedrich-Schiller-University Jena, 07743 Jena, Germany
⁵Leibniz Institute of Photonic Technology e.V., 07745 Jena, Germany
⁶MRC Human Immunology Unit and Wolfson Imaging Centre Oxford, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom
⁷Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, PL-01-224 Warsaw, Poland
⁸Group for Computational Life Sciences, Division of Physical Chemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia

^*Corresponding author: smith@physik.fau.de

Article Text

Click to Expand

Supplemental Material

Click to Expand

References

Click to Expand

Issue

Vol. 3, Iss. 4 — October - December 2021

Subject Areas

Reuse & Permissions

Author publication services for translation and copyediting assistance advertisement

Images

Figure 1
(a) Experimental image of an actin network bounded to Lo or Ld anchors (Lo or Ld pinning). The membrane was stained by a Ld marker (magenta) and the actin network by a green marker. The rightmost panel shows an overlay of both markers. The phases induced on the membrane bridge the gaps between the anchors. The image was taken below the critical temperature $T_{c}$ of a bare membrane (for the control panels, see the Supplemental Material [29] as well as [28]). Similar domains have also been observed above $T_{c}$ [28]. (b) Schematic illustration of the experimental system. The actin fiber is pinned to the membrane with streptavidins (yellow) that are anchored to either Lo or Ld lipids. The anchors induce local demixing (magenta) of the membrane. (c) Schematic illustration of the mechanism of formation of the lipid domains in the membrane discussed in this paper. Depending on the sign of the excess hydrophobic mismatch ${\bar{h}}_{0}$ , the lipid composition around the anchor will preferentially be in one of the two phases (Lo or Ld), represented here by the mixtures of blue and yellow lipids. In the theoretical model, the phase is characterized by the sign of the composition order parameter $ϕ$ . Away from the critical point of demixing, the domain size is of the order of the correlation length $ξ$ at the dimensionless temperature $τ$ as defined in the text.
Reuse & Permissions
Figure 2
Zones of the model. The top-left panel presents the space of parameters. The average OPs $〈 h 〉$ and $〈 ϕ 〉$ , and their amplitudes $h_{amp}$ and $ϕ_{amp}$ multiplying the leading-order exponential decay for large distances, are shown in the other three panels. All functions have been calculated for $κ = 10$ for the points in the space of parameters indicated by arrows. Gray vertical lines on the plots of average OPs indicate the size $ρ_{ϕ}$ of the formed domains.
Reuse & Permissions
Figure 3
Mean membrane composition $〈 ϕ 〉$ around a linear arrangement of four membrane inclusions, calculated from the theoretical model for $ω = κ μ^{2} = 2.5$ and two different values of $τ$ . All lengths are given in units of $ζ$ . The positions of the inclusions are marked by green dots. Contour lines are shown for $〈 ϕ 〉 = 0$ (dotted), $〈 ϕ 〉 = \pm 0.5$ (dot-dashed), $〈 ϕ 〉 = \pm 1$ (dashed), and $〈 ϕ 〉 = \pm 1.5$ (solid). The color code is motivated by the colors used in the experiment: for positive mismatch ${\bar{h}}_{0} = + 1$ (left column) it represents the Ld marker with Lo pinning, whereas for negative mismatch ${\bar{h}}_{0} = - 1$ (right column) it represents the Ld marker using Ld pinning. The two color codes are used as the homogeneous phase in the experiment has a different color depending on the type of pinning. A possible actin overlay is shown in the lower left panel with green. Upon approaching the critical temperature, the domains of the $ϕ$ field around the pinning points grow in size, and finally merge forming a bridge that connects all the actin pinning points.
Reuse & Permissions

Physical Review Research