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Open Access Publications from the University of California

Scholarly Works (2 results)

  • Thesis
  • Peer Reviewed
UC Berkeley Electronic Theses and Dissertations (2013)

In this work we use mesoscopic simulation to investigate the short and medium range interaction of transmembrane helices. First, we develop a coarse-grained model of a generic transmembrane α-helix. We use the geometry constraints of an α-helix, along with a set

of homogeneous hydrophobic beads. We discuss the reasoning behind this modeling and why various other plausible models have failed in describing the short-range interactions of transmembrane helices.

We then show the effect of hydrophobic mismatch on these model helices. The tilt angle of a single helix is affected by its hydrophobic mismatch with the surrounding bilayer. We show that the hydrophobic mismatch, via its effect on the tilt angle, has a crucial effect on the cross angle of two packed transmembrane helices as well.

We further show the effect of hydrophobic mismatch on the potential of mean force between the helices as well as on the thickness and tilt angle of the lipids surrounding the helices. We introduce a class of especially long helices, termed super-positive mismatched

helices, to which the response of the lipids differs and discuss the origin of this behavior.

These coarse-grained simulations are performed using the Dissipative Particle Dynamics (DPD) scheme Performing large time and length scale simulations using this scheme is highly CPU-time consuming. To enhance our simulation capabilities we develop a novel, massively parallel simulation algorithm. We introduce this algorithm and the original concepts we developed for parallelizing the DPD scheme. We show that this novel approach provides

up to 30 times speed up on a Graphical Processing Unit (GPU) over the non-parallel CPU version.

Finally, we use our parallel algorithm to perform simulation on a large time and length scale system. We investigate the effect of Cholesterol on the bending rigidity of lipid bilayers and show the effect of a phase transition on the bending modulus. Extracting the bending modulus from simulation requires a large system that enables long-range height fluctuations. Using a fast, parallel simulation algorithm for such a task is therefore crucial.

    Cover page: Molecular Simulations of Lipid Bilayers and Membrane Helices Interactions
    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2014)
    Large scale changes to lipid bilayer shapes are well represented by the Helfrich model. However, there are membrane processes that take place at smaller length scales that this model cannot address. In this work, we present a one-dimensional continuum model that captures the mechanics of the lipid bilayer membrane at the length scale of the lipids themselves. The model is developed using the Cosserat theory of surfaces with lipid orientation, or 'tilt', as the fundamental degree of freedom. The Helfrich model can be recovered as a special case when the curvatures are small and the lipid tilt is everywhere zero. We use the tilt model to study local membrane deformations in response to a protein inclusion. Parameter estimates and boundary conditions are obtained from a coarse-grained molecular model using dissipative particle dynamics (DPD) to capture the same phenomenon. The continuum model is able to reproduce the membrane bending, stretch and lipid tilt as seen in the DPD model. The lipid tilt angle relaxes to the bulk tilt angle within 5-6 nm from the protein inclusion. Importantly, for large tilt gradients induced by the proteins, the tilt energy contribution is larger than the bending energy contribution. Thus, the continuum model of tilt accurately captures behaviors at length scales shorter than the membrane thickness.
      Cover page: Small scale membrane mechanics
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