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Open Access Publications from the University of California

Scholarly Works (6 results)

  • Thesis
  • Peer Reviewed
UC Berkeley Electronic Theses and Dissertations (2015)

Lipid bilayers, along with embedded inclusions such as cholesterol and proteins, constitute a biological membrane—the interface between a cell or organelle and its environment. Understanding the structure of a biological membrane and the physical principles responsible for the organization of membrane inclusions is crucial to understanding the processes that occur on the surface of a cell or organelle such as inter-cellular signaling, immune synapse processes, exo- and endocytosis, and membrane fusion. In this work, we study the organization and effect of inclusions in a lipid bilayer using statistical mechanics principles and large-scale molecular simulations.

In the first part of this work, we propose a generic physical force for the assembly of inclusions in lipid bilayers—the orderphobic effect. Inspired by modern theories of the hydrophobic effect, this force is governed by the physics of the first-order phase transition between the ordered (i.e., solid-like) and disordered (i.e., fluid) phases of lipid bilayers. We show the existence and nature of this force using coarse-grained molecular dynamics simulations, and demonstrate the lateral assembly of two model proteins, or ‘orderphobes’, within a lipid bilayer. The effect is powerful and operates at nano- to mesoscopic scales, and could be a potential explanation for the clustering of proteins in a biological membrane.

In the second part of this work, we focus on hydrophobic inclusions within the lipid bilayer that give rise to organelles known as lipid droplets. These droplets, earlier thought to be passive stores of hydrophobic material in an otherwise aqueous cytosol, have now been implicated in various metabolic diseases. Since the growth and behavior of nascent droplets is sub-microscopic, little is known about the details of this process. We construct a computational framework that allows for a lipid reservoir to study asymmetric inclusions in a lipid bilayer such as the lipid droplet. Further, we identify key stages in the growth and budding of this organelle.

    Cover page: Physical Considerations of the Organization of Inclusions in Lipid Bilayer Systems
    • Article
    • Peer Reviewed
    UC Berkeley Previously Published Works (2018)
    We demonstrate pretransition effects in space-time in trajectories of systems in which the dynamics displays a first-order phase transition between distinct dynamical phases. These effects are analogous to those observed for thermodynamic first-order phase transitions, most notably the hydrophobic effect in water. Considering the (infinite temperature) East model as an elementary example, we study the properties of "space-time solvation" by examining trajectories where finite space-time regions are conditioned to be inactive in an otherwise active phase. We find that solvating an inactive region of space-time within an active trajectory shows two regimes in the dynamical equivalent of solvation free energy: an "entropic" small solute regime in which uncorrelated fluctuations are sufficient to evacuate activity from the solute, and an "energetic" large solute regime which involves the formation of a solute-induced inactive domain with an associated active-inactive interface bearing a dynamical interfacial tension. We also show that as a result of this dynamical interfacial tension there is a dynamical analog of the hydrophobic collapse that drives the assembly of large hydrophobes in water. We discuss the general relevance of these results to the properties of dynamical fluctuations in systems with slow collective relaxation such as glass formers.
      Cover page: Solvation in Space-time: Pretransition Effects in Trajectory Space
      • Article
      • Peer Reviewed
      UC Berkeley Previously Published Works (2019)
      We present a model for glassy dynamics in supercooled liquid mixtures. Given the relaxation behavior of individual supercooled liquids, the model predicts the relaxation times of their mixtures as temperature is decreased. The model is based on dynamical facilitation theory for glassy dynamics, which provides a physical basis for relaxation and vitrification of a supercooled liquid. This is in contrast to empirical linear interpolations such as the Gordon-Taylor equation typically used to predict glass transition temperatures of liquid mixtures. To understand the behavior of supercooled liquid mixtures we consider a multicomponent variant of the kinetically constrained East model in which components have a different energy scale and can also diffuse when locally mobile regions, i.e., excitations, are present. Using a variational approach we determine an effective single component model with a single effective energy scale that best approximates a mixture. When scaled by this single effective energy, we show that experimental relaxation times of many liquid mixtures all collapse onto the "parabolic law" predicted by dynamical facilitation theory. The model can be used to predict transport properties and glass transition temperatures of mixtures of glassy materials, with implications in atmospheric chemistry, biology, and pharmaceuticals.
        Cover page: Theory for Glassy Behavior of Supercooled Liquid Mixtures
        • Article
        • Peer Reviewed
        UC Berkeley Previously Published Works (2015)
        We characterize the order-disorder transition in a model lipid bilayer using molecular dynamics simulations. We find that the ordered phase is hexatic. In particular, in-plane structures possess a finite concentration of 5-7 disclination pairs that diffuse throughout the plane of the bilayer, and further, in-plane structures exhibit long-range orientational order and short-range translational order. In contrast, the disordered phase is liquid. The transition between the two phases is first order. Specifically, it exhibits hysteresis, and coexistence exhibits an interface with capillary scaling. The location of the interface and its spatial fluctuations are analyzed with a spatial field constructed from a rotational-invariant for local 6-fold orientational order. As a result of finite interfacial tension, there necessarily exist associated forces of assembly between membrane-bound solutes that pre-melt the ordered phase.
          Cover page: The order-disorder transition in model lipid bilayers is a first-order hexatic to liquid phase transition
          • Article
          • Peer Reviewed
          UC Berkeley Previously Published Works (2016)
          We present a mechanism for a generic and powerful force of assembly and mobility for transmembrane proteins in lipid bilayers. This force is a pre-transition (or pre-melting) effect for the first-order transition between ordered and disordered phases in the host membrane. Using large scale molecular simulation, we show that a protein with hydrophobic thickness equal to that of the disordered phase embedded in an ordered bilayer stabilizes a microscopic order-disorder interface, and the stiffness of that interface is finite. When two such proteins approach each other, they assemble because assembly reduces the net interfacial free energy. In analogy with the hydrophobic effect, we refer to this phenomenon as the "orderphobic effect". The effect is mediated by proximity to the order-disorder phase transition and the size and hydrophobic mismatch of the protein. The strength and range of forces arising from the orderphobic effect are significantly larger than those that could arise from membrane elasticity for the membranes we examine.
            • Article
            • Peer Reviewed
            UC Berkeley Previously Published Works (2016)
            We present a mechanism for a generic, powerful force of assembly and mobility for transmembrane proteins in lipid bilayers. This force is a pre-transition (or pre-melting) effect for the first-order transition between ordered and disordered phases in the membrane. Using large-scale molecular simulation, we show that a protein with hydrophobic thickness equal to that of the disordered phase embedded in an ordered bilayer stabilizes a microscopic order-disorder interface. The stiffness of that interface is finite. When two such proteins approach each other, they assemble because assembly reduces the net interfacial energy. Analogous to the hydrophobic effect, we refer to this phenomenon as the 'orderphobic effect'. The effect is mediated by proximity to the order-disorder phase transition and the size and hydrophobic mismatch of the protein. The strength and range of forces arising from this effect are significantly larger than those that could arise from membrane elasticity for the membranes considered.
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