Lipid membranes between nano and micro:

Lipid membranes between nano and micro: A solvent-free coarse-grained simulation model (and what we can learn from it) Markus Deserno Max-Planck-Institut für Polymerforschung, Mainz http://www.mpip-mainz.mpg.de/~deserno deserno@mpip-mainz.mpg.de Cells and Materials, Workshop I: Membrane Protein Science and Engineering IPAM, Los Angeles, California, USA

Motivation

Motivation Cells !

Motivation Cells & Materials !

Motivation ? Cells & Materials

Some simple scaling

Some simple scaling Thickness: 5 nm

Lipids ~ dense hydrocarbons ~ typical length scale: 5 nm ~ between rubber and plastic ~ Young modulus: Some simple scaling Thickness: 5 nm

Some simple scaling

membrane thickness bending modulus Young’s modulus Some simple scaling

membrane thickness bending modulus Young’s modulus Some simple scaling That’s about right!

Implications Bending modulus of phospholipid bilayers: a few tens of kT Why’s that such an interesting value?

bigger than thermal energy Bilayer doesn’t fluctuate into pieces! Implications Bending modulus of phospholipid bilayers: a few tens of kT Why’s that such an interesting value?

bigger than thermal energy Bilayer doesn’t fluctuate into pieces! • not much bigger than thermal energy Nano-sources of energy can deform it! Implications Bending modulus of phospholipid bilayers: a few tens of kT Why’s that such an interesting value?

bigger than thermal energy Bilayer doesn’t fluctuate into pieces! • not much bigger than thermal energy Nano-sources of energy can deform it! Implications Bending modulus of phospholipid bilayers: a few tens of kT Why’s that such an interesting value? Ideal material for nano-technology !

But front-cover “NanoTech” seems to be shiny metal stuff!

But front-cover “NanoTech” seems to be shiny metal stuff! Just turn the argument around:

But front-cover “NanoTech” seems to be shiny metal stuff! Just turn the argument around: (metal)

But front-cover “NanoTech” seems to be shiny metal stuff! Just turn the argument around: falls apart ! (metal)

But front-cover “NanoTech” seems to be shiny metal stuff! Nanotechnology invariably means soft matter! Just turn the argument around: falls apart ! (metal)

Nature has found out first! Membranes everywhere !

Self-assembly Protein-embedding Fluidity Pressure-profiles Bending-deformations A closer look… Lipid bilayers show interesting physics on many different length scales. J. Gould and W. Keeton, Biological Science, 6th ed. (W.W. Norton, New York, 1996)

A closer look… Lipid bilayers show interesting physics on many different length scales. J. Gould and W. Keeton, Biological Science, 6th ed. (W.W. Norton, New York, 1996) When studying this system, one’s approach should be tuned towards the length scale one intends to probe.

any A closer look… Lipid bilayers show interesting physics on many different length scales. J. Gould and W. Keeton, Biological Science, 6th ed. (W.W. Norton, New York, 1996) When studying this system, one’s approach should be tuned towards the length scale one intends to probe.

any Theory A closer look… Lipid bilayers show interesting physics on many different length scales. J. Gould and W. Keeton, Biological Science, 6th ed. (W.W. Norton, New York, 1996) When studying this system, one’s approach should be tuned towards the length scale one intends to probe.

any Theory Simulation A closer look… Lipid bilayers show interesting physics on many different length scales. J. Gould and W. Keeton, Biological Science, 6th ed. (W.W. Norton, New York, 1996) When studying this system, one’s approach should be tuned towards the length scale one intends to probe.

Experiment any Theory Simulation A closer look… Lipid bilayers show interesting physics on many different length scales. J. Gould and W. Keeton, Biological Science, 6th ed. (W.W. Norton, New York, 1996) When studying this system, one’s approach should be tuned towards the length scale one intends to probe.

much detail little detail i n c r e a s i n g l y c o a r s e g r a i n e d atomistic models bead-spring models triangulated surfaces increasing numerical efficiency matter of debate… Simulation of lipid membranes Marrink; Klein, Sansom; Scott; Voth; … Gompper&Kroll,… “standard” Lennard-Jones DPD solvent free Groot&Rabone; Shillcock&Lipowsky; Laradji&Kumar, … Drouffe&Maggs&Leibler; Noguchi&Takasu; Farago; Brannigan&Brown Goetz&Lipowsky; Stevens; …

Why is “solvent free” good?

membrane surface Why is “solvent free” good?

membrane surface solvent bulk Why is “solvent free” good?

membrane surface solvent bulk Why is “solvent free” good? Studying membranes may well become the study of a finite size effect!

membrane surface solvent bulk M. Laradji, P. B. Sunil Kumar, Phys. Rev. Lett. 93, 198105 (2004) Illustrative example 16000 (DPD) lipids times 4 beads per lipid  64000 degrees of freedom for lipids But in total: 1536000 particles in box  96% of simulation time spent with solvent!

Implicit solvent models are very common and incredibly useful in polymer physics. Why are they not so common in the membrane field? “No solvent” is difficult. Why?

Implicit solvent models are very common and incredibly useful in polymer physics. Why are they not so common in the membrane field? Polymers don’t first have to self-assemble “No solvent” is difficult. Why?

Implicit solvent models are very common and incredibly useful in polymer physics. Why are they not so common in the membrane field? Polymers don’t first have to self-assemble One needs to introduce additional cohesive energy for the lipid tails! “No solvent” is difficult. Why?

Implicit solvent models are very common and incredibly useful in polymer physics. Why are they not so common in the membrane field? Polymers don’t first have to self-assemble kBT, not eV! One needs to introduce additional cohesive energy for the lipid tails! “No solvent” is difficult. Why?

Implicit solvent models are very common and incredibly useful in polymer physics. Why are they not so common in the membrane field? Polymers don’t first have to self-assemble kBT, not eV! One needs to introduce additional cohesive energy for the lipid tails! Fluidity has proven to be the main challenge “No solvent” is difficult. Why?

weak attraction “gas” phase strong attraction solid bilayer Difficulties Polymers don’t first have to self-assemble Fluidity has proven to be the main challenge Empirical observation:

weak attraction “gas” phase no fluid phase inbetween! strong attraction solid bilayer Difficulties Polymers don’t first have to self-assemble Fluidity has proven to be the main challenge Empirical observation:

weak attraction “gas” phase no fluid phase inbetween! strong attraction solid bilayer Difficulties Polymers don’t first have to self-assemble Fluidity has proven to be the main challenge Empirical observation: This observation is incorrect. But we’ll later see where it came from!

Previous and current solutions • J.-M. Drouffe, A. C. Maggs, and S. Leibler, Science 254, 1353 (1991) • H. Noguchi and M. Takasu, Phys. Rev. E 64, 041913(2001) • Z.J. Wang and D. Frenkel, J. Chem. Phys. 122, 234711 (2005) • H. Noguchi and G. Gompper, Phys. Rev. E 72, 021903 (2006) • G. Ayton and G.A. Voth, Biophys. J. 83, 3357 (2002) • O. Farago, J. Chem. Phys. 119, 396 (2003) • G. Brannigan and F.L.H. Brown, J. Chem. Phys. 120, 1059 (2004) • I.R. Cooke, K. Kremer, M. Deserno, Phys. Rev. E 72, 011506 (2005) • G. Brannigan, P.F. Philips, and F.L.H. Brown, Phys. Rev. E 72, 011915, (2005)

Lipid membranes between nano and micro: