Measuring Pico-Newton Forces with Lipid Anchors As Force Sensors in Molecular Dynamics Simulations

Overview

Journal J Phys Chem B

Publisher American Chemical Society

Specialty Chemistry

Date 2023 May 1

PMID 37127845

Authors

Batuhan Kav

Thomas R Weikl

Emanuel Schneck

Affiliations

Soon will be listed here.

Abstract

Binding forces between biomolecules are ubiquitous in nature but sometimes as weak as a few pico-Newtons (pN). In many cases, the binding partners are attached to biomembranes with the help of a lipid anchor. One important example are glycolipids that promote membrane adhesion through weak carbohydrate-carbohydrate binding between adjacent membranes. Here, we use molecular dynamics (MD) simulations to quantify the forces generated by bonds involving membrane-anchored molecules. We introduce a method in which the protrusion of the lipid anchors from the membrane acts as the force sensor. Our results with two different glycolipids reveal binding forces of up to 20 pN and corroborate the recent notion that carbohydrate-carbohydrate interactions are generic rather than specific.

References

Marrink S, Berger O, Tieleman P, Jahnig F . Adhesion forces of lipids in a phospholipid membrane studied by molecular dynamics simulations. Biophys J. 1998; 74(2 Pt 1):931-43. PMC: 1302572. DOI: 10.1016/S0006-3495(98)74016-0. View

Garcia A, Vega M, Boettiger D . Modulation of cell proliferation and differentiation through substrate-dependent changes in fibronectin conformation. Mol Biol Cell. 1999; 10(3):785-98. PMC: 25202. DOI: 10.1091/mbc.10.3.785. View

Misevic G, Finne J, Burger M . Involvement of carbohydrates as multiple low affinity interaction sites in the self-association of the aggregation factor from the marine sponge Microciona prolifera. J Biol Chem. 1987; 262(12):5870-7. View

Honarmandi P, Lee H, Lang M, Kamm R . A microfluidic system with optical laser tweezers to study mechanotransduction and focal adhesion recruitment. Lab Chip. 2010; 11(4):684-94. DOI: 10.1039/c0lc00487a. View

Chen L . Exploring the free-energy landscapes of biological systems with steered molecular dynamics. Phys Chem Chem Phys. 2011; 13(13):6176-83. PMC: 3111135. DOI: 10.1039/c0cp02799e. View

Dickson C, Madej B, Skjevik A, Betz R, Teigen K, Gould I . Lipid14: The Amber Lipid Force Field. J Chem Theory Comput. 2014; 10(2):865-879. PMC: 3985482. DOI: 10.1021/ct4010307. View

Lorenz B, Alvarez de Cienfuegos L, Oelkers M, Kriemen E, Brand C, Stephan M . Model system for cell adhesion mediated by weak carbohydrate-carbohydrate interactions. J Am Chem Soc. 2012; 134(7):3326-9. PMC: 3288207. DOI: 10.1021/ja210304j. View

Tieleman D, Marrink S . Lipids out of equilibrium: energetics of desorption and pore mediated flip-flop. J Am Chem Soc. 2006; 128(38):12462-7. DOI: 10.1021/ja0624321. View

Hummer G, Szabo A . Kinetics from nonequilibrium single-molecule pulling experiments. Biophys J. 2003; 85(1):5-15. PMC: 1303060. DOI: 10.1016/S0006-3495(03)74449-X. View

10.

Pieffet G, Botero A, Peters G, Forero-Shelton M, Leidy C . Exploring the local elastic properties of bilayer membranes using molecular dynamics simulations. J Phys Chem B. 2014; 118(45):12883-91. DOI: 10.1021/jp504427a. View

11.

van der Spoel D, Lindahl E, Hess B, Groenhof G, Mark A, Berendsen H . GROMACS: fast, flexible, and free. J Comput Chem. 2005; 26(16):1701-18. DOI: 10.1002/jcc.20291. View

12.

Kucerka N, Nieh M, Katsaras J . Fluid phase lipid areas and bilayer thicknesses of commonly used phosphatidylcholines as a function of temperature. Biochim Biophys Acta. 2011; 1808(11):2761-71. DOI: 10.1016/j.bbamem.2011.07.022. View

13.

Risselada H, Bubnis G, Grubmuller H . Expansion of the fusion stalk and its implication for biological membrane fusion. Proc Natl Acad Sci U S A. 2014; 111(30):11043-8. PMC: 4121774. DOI: 10.1073/pnas.1323221111. View

14.

Grubmuller H, Heymann B, Tavan P . Ligand binding: molecular mechanics calculation of the streptavidin-biotin rupture force. Science. 1996; 271(5251):997-9. DOI: 10.1126/science.271.5251.997. View

15.

Bucior I, Scheuring S, Engel A, Burger M . Carbohydrate-carbohydrate interaction provides adhesion force and specificity for cellular recognition. J Cell Biol. 2004; 165(4):529-37. PMC: 2172358. DOI: 10.1083/jcb.200309005. View

16.

Paulick M, Bertozzi C . The glycosylphosphatidylinositol anchor: a complex membrane-anchoring structure for proteins. Biochemistry. 2008; 47(27):6991-7000. PMC: 2663890. DOI: 10.1021/bi8006324. View

17.

Blakely B, Dumelin C, Trappmann B, McGregor L, Choi C, Anthony P . A DNA-based molecular probe for optically reporting cellular traction forces. Nat Methods. 2014; 11(12):1229-32. PMC: 4247985. DOI: 10.1038/nmeth.3145. View

18.

Nussinov R, Tsai C, Jang H . Ras assemblies and signaling at the membrane. Curr Opin Struct Biol. 2020; 62:140-148. DOI: 10.1016/j.sbi.2020.01.009. View

19.

Sheridan S, Grater F, Daday C . How Fast Is Too Fast in Force-Probe Molecular Dynamics Simulations?. J Phys Chem B. 2019; 123(17):3658-3664. DOI: 10.1021/acs.jpcb.9b01251. View

20.

Rick S . A reoptimization of the five-site water potential (TIP5P) for use with Ewald sums. J Chem Phys. 2004; 120(13):6085-93. DOI: 10.1063/1.1652434. View