About

Frank Brown is a Professor in the Department of Physics at UC Santa Barbara, located in Chem 4126. His research focuses on the Physics of Soft and Living Matter. The page text does not provide further detailed information about his specific research projects, background, or key contributions beyond his association with this field.

Research topics

• Statistical physics
• Mechanics
• Physics
• Thermodynamics
• Chemistry
• Computer Science
• Biological system
• Biology
• Optics
• Biophysics
• Classical mechanics
• Chromatography
• Chemical physics
• Quantum mechanics

Selected publications

• Dynamic correlations in lipid bilayer membranes over finite time intervals

  The Journal of Chemical Physics · 2023 · 1 citations

  Senior authorCorresponding
  • Computer Science
  • Physics
  • Chemistry

  Recent single-molecule measurements [Schoch et al., Proc. Natl. Acad. Sci. U. S. A. 118, e2113202118 (2021)] have observed dynamic lipid-lipid correlations in membranes with submicrometer spatial resolution and submillisecond temporal resolution. While short from an instrumentation standpoint, these length and time scales remain long compared to microscopic molecular motions. Theoretical expressions are derived to infer experimentally measurable correlations from the two-body diffusion matrix appropriate for membrane-bound bodies coupled by hydrodynamic interactions. The temporal (and associated spatial) averaging resulting from finite acquisition times has the effect of washing out correlations as compared to naive predictions (i.e., the bare elements of the diffusion matrix), which would be expected to hold for instantaneous measurements. The theoretical predictions are shown to be in excellent agreement with Brownian dynamics simulations of experimental measurements. Numerical results suggest that the experimental measurement of membrane protein diffusion, in complement to lipid diffusion measurements, might help to resolve the experimental ambiguities encountered for certain black lipid membranes.

  PublisherDOI

• Correlated diffusion in lipid bilayers

  Proceedings of the National Academy of Sciences · 2021 · 18 citations

  • Statistical physics
  • Chemical physics
  • Classical mechanics

  Lipid membranes are complex quasi-two-dimensional fluids, whose importance in biology and unique physical/materials properties have made them a major target for biophysical research. Recent single-molecule tracking experiments in membranes have caused some controversy, calling the venerable Saffman-Delbrück model into question and suggesting that, perhaps, current understanding of membrane hydrodynamics is imperfect. However, single-molecule tracking is not well suited to resolving the details of hydrodynamic flows; observations involving correlations between multiple molecules are superior for this purpose. Here dual-color molecular tracking with submillisecond time resolution and submicron spatial resolution is employed to reveal correlations in the Brownian motion of pairs of fluorescently labeled lipids in membranes. These correlations extend hundreds of nanometers in freely floating bilayers (black lipid membranes) but are severely suppressed in supported lipid bilayers. The measurements are consistent with hydrodynamic predictions based on an extended Saffman-Delbrück theory that explicitly accounts for the two-leaflet bilayer structure of lipid membranes.

  PublisherOA PDFDOI

• Integrated rate laws for processive and distributive enzymatic turnover

  The Journal of Chemical Physics · 2019-06-28 · 1 citations

  articleSenior author

  Recently derived steady-state differential rate laws for the catalytic turnover of molecules containing two substrate sites are reformulated as integrated rate laws. The analysis applies to a broad class of Markovian dynamic models, motivated by the varied and often complex mechanisms associated with DNA modifying enzymes. Analysis of experimental data for the methylation kinetics of DNA by Dam (DNA adenine methyltransferase) is drastically improved through the use of integrated rate laws. Data that are too noisy for fitting to differential predictions are reliably interpreted through the integrated rate laws.

  PublisherDOI

• Lipid diffusion in the distal and proximal leaflets of supported lipid bilayer membranes studied by single particle tracking

  The Journal of Chemical Physics · 2018-03-09 · 43 citations

  article

  Supported lipid bilayers (SLBs) have been studied extensively as simple but powerful models for cellular membranes. Yet, potential differences in the dynamics of the two leaflets of a SLB remain poorly understood. Here, using single particle tracking, we obtain a detailed picture of bilayer dynamics. We observe two clearly separate diffusing populations, fast and slow, that we associate with motion in the distal and proximal leaflets of the SLB, respectively, based on fluorescence quenching experiments. We estimate diffusion coefficients using standard techniques as well as a new method based on the blur of images due to motion. Fitting the observed diffusion coefficients to a two-leaflet membrane hydrodynamic model allows for the simultaneous determination of the intermonolayer friction coefficient and the substrate-membrane friction coefficient, without any prior assumptions on the strengths of the relevant interactions. Remarkably, our calculations suggest that the viscosity of the interfacial water confined between the membrane and the substrate is elevated by ∼104 as compared to bulk water. Using hidden Markov model analysis, we then obtain insight into the transbilayer movement of lipids. We find that lipid flip-flop dynamics are very fast, with half times in the range of seconds. Importantly, we find little evidence for membrane defect mediated lipid flip-flop for SLBs at temperatures well above the solid-to-liquid transition, though defects seem to be involved when the SLBs are cooled down. Our work thus shows that the combination of single particle tracking and advanced hydrodynamic modeling provides a powerful means to obtain insight into membrane dynamics.

  PublisherDOI

• Surfactant pK a Calculations using Molecular Dynamics Simulations

  Biophysical Journal · 2017-02-01

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Specificity versus Processivity in the Sequential Modification of DNA: A Study of DNA Adenine Methyltransferase

  The Journal of Physical Chemistry B · 2017-12-20 · 6 citations

  articleSenior author

  A detailed analysis is carried out on both published experimental results and new experiments for the methylation kinetics of two-site DNA substrates (with site separations between 100 and 800 bp) catalyzed by bacterial DNA adenine methyltransferase (Dam). A previously reported rate enhancement for the second methylation event (relative to that of the first methylation) is shown to result from elevated substrate specificity for singly methylated DNA over that of unmethylated DNA and not processive turnover of both sites by the same copy of Dam. An elementary model is suggested that cleanly fits the experimental data over a broad range of intersite separations. The model hypothesizes a looping mediated interference between competing unmethylated Dam sites on the same DNA strand.

  PublisherDOI

• On the generality of Michaelian kinetics

  The Journal of Chemical Physics · 2017-01-03 · 8 citations

  articleSenior author

  The reversible Michaelis-Menten equation is shown to follow from a very broad class of steady-state kinetic models involving enzymes that adopt a unique free (i.e., not complexed to substrate/product) state in solution. In the case of enzymes with multiple free states/conformations (e.g., fluctuating, hysteretic, or co-operative monomeric enzymes), Michaelian behavior is still assured if the relative steady-state populations of free enzyme states are independent of substrate and product concentration. Prior models for Michaelian behavior in multiple conformer enzymes are shown to be special cases of this single condition.

  PublisherDOI

• Lipid and Peptide Diffusion in Bilayers: The Saffman–Delbrück Model and Periodic Boundary Conditions

  The Journal of Physical Chemistry B · 2016-12-14 · 123 citations

  articleOpen access

  The periodic Saffman–Delbrück (PSD) model, an extension of the Saffman–Delbrück model developed to describe the effects of periodic boundary conditions on the diffusion constants of lipids and proteins obtained from simulation, is tested using the coarse-grained Martini and all-atom CHARMM36 (C36) force fields. Simulations of pure Martini dipalmitoylphosphatidylcholine (DPPC) bilayers and those with one embedded gramicidin A (gA) dimer or one gA monomer with sizes ranging from 512 to 2048 lipids support the PSD model. Underestimates of D∞ (the value of the diffusion constant for an infinite system) from the 512-lipid system are 35% for DPPC, 45% for the gA monomer, and 70% for the gA dimer. Simulations of all-atom DPPC and dioleoylphosphatidylcholine (DOPC) bilayers yield diffusion constants not far from experiment. However, the PSD model predicts that diffusion constants at the sizes of the simulation should underestimate experiment by approximately a factor of 3 for DPPC and 2 for DOPC. This likely implies a deficiency in the C36 force field. A Bayesian method for extrapolating diffusion constants of lipids and proteins in membranes obtained from simulation to infinite system size is provided.

  PublisherOA PDFDOI

• Extracting Enzyme Processivity from Kinetic Assays

  Biophysical Journal · 2016-02-01

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Strong influence of periodic boundary conditions on lateral diffusion in lipid bilayer membranes

  The Journal of Chemical Physics · 2015-10-16 · 118 citations

  articleSenior author

  The Saffman-Delbrück hydrodynamic model for lipid-bilayer membranes is modified to account for the periodic boundary conditions commonly imposed in molecular simulations. Predicted lateral diffusion coefficients for membrane-embedded solid bodies are sensitive to box shape and converge slowly to the limit of infinite box size, raising serious doubts for the prospects of using detailed simulations to accurately predict membrane-protein diffusivities and related transport properties. Estimates for the relative error associated with periodic boundary artifacts are 50% and higher for fully atomistic models in currently feasible simulation boxes. MARTINI simulations of LacY membrane protein diffusion and LacY dimer diffusion in DPPC membranes and lipid diffusion in pure DPPC bilayers support the underlying hydrodynamic model.

  PublisherDOI

Recent grants

• Stochastic methods in chemistry and biophysics

  NSF · $569k · 2012–2016

• Theoretical methods in chemistry and biophysics

  NSF · $600k · 2015–2019

• CAREER: Stochastic methods in chemistry and biophysics

  NSF · $509k · 2004–2009

• Acquisition of a High Performance Central Computing Facility at UCSB

  NSF · $444k · 2003–2006

• Stochastic methods in chemistry and biophysics

  NSF · $435k · 2009–2014

Frequent coauthors

• Brian A. Camley

  Johns Hopkins University

  17 shared

• Max C. Watson

  NIST Center for Neutron Research

  12 shared

• Grace Brannigan

  Rutgers, The State University of New Jersey

  10 shared

• Lawrence C.-L. Lin

  9 shared

• Yujun Zheng

  Shandong University

  9 shared

• Richard W. Pastor

  8 shared

• Kent R. Wilson

  8 shared

• Golan Bel

  7 shared

Labs

• Frank Brown's LabPI

  Not provided