The Effective Field Theory approach towards membrane-mediated interactions between particles

Yolcu, Cem; Haussman, Robert; Deserno, Markus

doi:10.1016/j.cis.2014.02.017

Cited by 54 publications

(59 citation statements)

References 94 publications

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“…In general, more than two membrane proteins are expected to interact in the crowded membrane environments provided by living cells. We have shown previously [89] that, in contrast to curvature-and fluctuationmediated protein interactions [51,52,55,61,63,64], bilayer thickness-mediated protein interactions are approximately pairwise additive, at least for large enough protein separations. For small protein separations, nonpairwise contributions to bilayer thickness-mediated interactions between integral membrane proteins can modify the interaction strength by > 1k B T [89].…”

Section: Discussionmentioning

confidence: 99%

“…(3) and modifications thereof have been found to capture the basic experimental phenomenology of bilayer-protein interactions in a wide range of experimental systems [4-11, 24-28, 31, 38-47, 81-83, 88-97], only involve parameters which can be measured directly in experiments, and are simple enough to allow analytic solutions. Analogous models have been formulated [7,48] to describe protein-induced curvature deformations [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64] and fluctuation-mediated interactions [49,[61][62][63][64][65][66][67][68]. In general, thickness-, curvature-, and fluctuation-mediated interactions all contribute to bilayer-mediated interactions between integral membrane proteins, but the relative strengths of these interactions depend on the specific experimental system under consideration.…”

Section: Discussionmentioning

confidence: 99%

“…(3) and the corresponding "zeroth-order" models [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68] capturing curvature-and fluctuation-mediated protein interactions absorb the molecular details of lipids and membrane proteins into effective material parameters. To provide a more detailed description of bilayer-protein interactions, a number of extensions and refinements of these models have been developed [44,45,[69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86].…”

Section: Discussionmentioning

confidence: 99%

“…According to this classic theory, membrane proteins may, in addition to thickness-mediated interactions [31,[39][40][41][42][43][44][45][46][47], also interact [7,48] via bilayer curvature deformations [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64] and bilayer fluctuations [49,[61][62][63][64][65][66][67][68]. While the competition between thickness-, curvature-, and fluctuation-mediated protein interactions depends on the properties of the specific lipids and membrane proteins under consideration, one generally expects [7,31] that thickness-mediated protein interactions are strong and short-ranged, and that curvature-and fluctuation-mediated protein interactions are weak and long-ranged.…”

Section: Introductionmentioning

confidence: 99%

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Bilayer-thickness-mediated interactions between integral membrane proteins

et al. 2016

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Hydrophobic thickness mismatch between integral membrane proteins and the surrounding lipid bilayer can produce lipid bilayer thickness deformations. Experiment and theory have shown that protein-induced lipid bilayer thickness deformations can yield energetically favorable bilayermediated interactions between integral membrane proteins, and large-scale organization of integral membrane proteins into protein clusters in cell membranes. Within the continuum elasticity theory of membranes, the energy cost of protein-induced bilayer thickness deformations can be captured by considering compression/expansion of the bilayer hydrophobic core, membrane tension, and bilayer bending, resulting in biharmonic equilibrium equations describing the shape of lipid bilayers for a given set of bilayer-protein boundary conditions. Here we develop a combined analytic and numerical methodology for the solution of the equilibrium elastic equations associated with protein-induced lipid bilayer deformations. Our methodology allows accurate prediction of thickness-mediated protein interactions for arbitrary protein symmetries at arbitrary protein separations and relative orientations. We provide exact analytic solutions for cylindrical integral membrane proteins with constant and varying hydrophobic thickness, and develop perturbative analytic solutions for noncylindrical protein shapes. We complement these analytic solutions, and assess their accuracy, by developing both finite element and finite difference numerical solution schemes. We provide error estimates of our numerical solution schemes and systematically assess their convergence properties. Taken together, the work presented here puts into place an analytic and numerical framework which allows calculation of bilayer-mediated elastic interactions between integral membrane proteins for the complicated protein shapes suggested by structural biology and at the small protein separations most relevant for the crowded membrane environments provided by living cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bilayer-thickness-mediated interactions between integral membrane proteins

et al. 2016

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“…Recent examples of the supra-coarse-grained approach include simulations of large-scale membrane remodelling by Bin-amphiphysin-Rvs (BAR) domains (Cui et al, 2013;Simunovic et al, 2013;Yu and Schulten, 2013), the membrane-induced formation of peptide fibrils (Morriss-Andrews et al, 2014) and the supra-molecular organization of photosynthetic membranes (Lee et al, 2015). Furthermore, the supra-coarse-grained approach allows for a natural connection to the macroscopic scale using, for instance, field-theory-or fluid-dynamics-based descriptions of cell membranes (Ayton et al, 2009;Camley and Brown, 2014;Fedosov et al, 2014;Yolcu et al, 2014).…”

Section: Supra Coarse-grain Resolutionmentioning

confidence: 99%

Computational ‘microscopy’ of cellular membranes

Ingólfsson

Arnarez²,

Periole³

et al. 2016

Journal of Cell Science

136

120

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Computational 'microscopy' refers to the use of computational resources to simulate the dynamics of a molecular system. Tuned to cell membranes, this computational 'microscopy' technique is able to capture the interplay between lipids and proteins at a spatiotemporal resolution that is unmatched by other methods. Recent advances allow us to zoom out from individual atoms and molecules to supramolecular complexes and subcellular compartments that contain tens of millions of particles, and to capture the complexity of the crowded environment of real cell membranes. This Commentary gives an overview of the main concepts of computational 'microscopy' and describes the state-of-the-art methods used to model cell membrane processes. We illustrate the power of computational modelling approaches by providing a few in-depth examples of largescale simulations that move up from molecular descriptions into the subcellular arena. We end with an outlook towards modelling a complete cell in silico.

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Biophysical Considerations in the Rational Design and Cellular Targeting of Flexible Polymeric Nanoparticles

Farokhirad

Kandy

Tsourkas

et al. 2021

Adv Materials Inter

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gene therapy [1][2][3] and their application as biomarkers for imaging and detection. [4][5][6] Functional nanoparticles are finding applications in genome editing, immune modulation, cell therapies, and molecular diagnostics to stratify patients based on biomarkers. However, the functional NPs' design, optimization, and deployment are hampered by our lack of understanding of their biological barriers and pharmacokinetics. [7] While such barriers have contributions that are systemic and span multiple scales, the specificity for a given application has essential contributions from the cellular scale. Cellular targeting is governed by avidity (adhesion) and uptake (internalization), which depend on the properties of the NPs and the cellular microenvironment.Adhesion between an NP and a cell surface typically involves the simultaneous binding [8,9] of many hundreds of ligands on the NP's surface to a similar number of receptors on the cell surface. [9][10][11][12][13] The physiological outcome of such multivalent adhesion, which can mediate diverse phenomena, including cell crowding and cell uptake, [14] depends on the strength of ligandreceptor binding interactions. Other factors that can modulate multivalent adhesion strength include physiochemical properties of both the NPs and the cell surfaces. [15] Previous How nanoparticle (NP) mechanical properties impact multivalent ligandreceptor-mediated binding to cell surfaces, the avidity, propensity for internalization, and effects due to crowding remains unknown or unquantified. Through computational analyses, the effects of NP composition from soft, deformable NPs to rigid spheres, effect of tethers, the crowding of NPs at the membrane surface, and the cell membrane properties such as cytoskeletal interactions are addressed. Analyses of binding mechanisms of three distinct NPs that differ in type and rigidity (core-corona flexible NP, rigid NP, and rigid-tethered NP) but are otherwise similar in size and ligand surface density are reported; moreover, for the case of flexible NP, NP stiffness is tuned by varying the internal crosslinking density. Biophysical modeling of NP binding to membranes together with thermodynamic analysis powered by free energy calculations is employed, and it is shown that efficient cellular targeting and uptake of NP functionalized with targeting ligand molecules can be shaped by factors including NP flexibility and crowding, receptor-ligand binding avidity, state of the membrane cytoskeleton, and curvature inducing proteins. Rational design principles that confer tension, membrane excess area, and cytoskeletal sensing properties to the NP which can be exploited for cellspecific targeting of NP are uncovered.

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The Effective Field Theory approach towards membrane-mediated interactions between particles

Cited by 54 publications

References 94 publications

Bilayer-thickness-mediated interactions between integral membrane proteins

Bilayer-thickness-mediated interactions between integral membrane proteins

Computational ‘microscopy’ of cellular membranes

Biophysical Considerations in the Rational Design and Cellular Targeting of Flexible Polymeric Nanoparticles

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