University of Minnesota
Department of Biomedical Engineering
http://www1.umn.edu/bme
612-624-4507

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Jonathan Sachs

Jonathan Sachs

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  • B.S., Mathematical Biochemistry, University of Michigan, 1996

  • Ph.D., Biomedical Engineering, Johns Hopkins University, 2003

  • NIH NRSA Postdoctoral Fellowship, Yale University, March 2004 - August 2006

Cellular Membrane Structure and Biophysics

Our interest is in the structural and dynamic properties of large-scale, self-assembled macromolecular complexes, such as biological membranes. As the fundamental component of sub-cellular organization, the membrane impacts nearly every aspect of cell biology: from cell growth and movement to signal transduction and intracellular transport of proteins. The membrane is composed of a surprisingly diverse array of lipid molecules that have the ability to self-assemble into a liquid-crystalline bilayer. The lipids provide more than a mere structural scaffold for the transmembrane protein machinery. By modulating the lipid composition of the bilayer, cells can fine-tune the protein environment and significantly affect protein function. We are interested in the specific, single-molecule chemical interactions within the membrane, and further, how the collective material properties of membranes, such as thickness and compressibility, result from the sum of these individual components. In order to engineer biomedical technologies that act at the membrane, it is important to understand how and in what circumstances the cell exploits these different levels of organization. Biophysical approaches to the study of membrane structure are especially fruitful in establishing the underlying principles of local and global bilayer organization. Computer simulations have traditionally been suited for chemical descriptions on the local level. Meanwhile, experiments have addressed the global level. Now, for the first time, advances in computer power and experimental techniques promise to transcend these limitations. It is our goal to combine computational simulations and experimentation in order to draw meaningful connections between the two levels.

Selected Publications

Lewis, A. K., Valley, C. C., and Sachs, J. N. (2012) TNFR1 signaling is associated with backbone conformational changes of receptor dimers consistent with over-activation in the R92Q TRAPS mutant, Biochemistry In Press.
 
Valley, C. C., and Cembran, A., and Lewis, A. K., and Gao, J., and Sachs, J.N. (2012) The methionine-aromatic motif plays a unique role in stabilizing protein structure, J. Biol. Chem In Press.
 
Valley, C.C., Lewis, A.K., Mudaliar, D.J., Perlmutter, J.D., Braun, A.R., Karim, C.B., Thomas, D.D, Brody, J.R. and Sachs, J.N. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces Death Receptor 5 networks that are highly organized. J Biol Chem. 2012 Jun 15;287(25):21265-78.
 
Braun, A.R., Sevcsik, E., Chin, P., Rhoades, E., Tristram-Nagle, S., and Sachs, J.N. α-Synuclein induces both positive mean curvature and negative Gaussian curvature in membranes. J Am Chem Soc. 2012 Feb 8; 134(5):2613-20.
 
Valley, C.C., Perlmutter, J.D., Braun, A.R., and Sachs, J.N. NaCl interactions with phosphatidylcholine bilayers do not alter membrane structure, but induce long-range ordering of ions and water. J Membrane Biology. 2011 Nov; 244(1):35-42.
 
Braun, A.R., Sachs, J.N. Extracting experimental measurables from molecular dynamics simulations of membranes. Annual Reports in Computational Chemistry, ARCC Vol 7, Chapter 6.
 
Perlmutter, J.D., Drasler W.J., Xie W., Gao J., Popot J.L., and Sachs J.N. All-atom and coarse-grained molecular dynamics simulations of a membrane protein stabilizing polymer. Langmuir. 2011 Sep 6;27(17):10523-37.
 
Perlmutter, J.D., Sachs, J.N. Inter-Leaflet Interaction and Asymmetry in Phase Separated Lipid Bilayers: Molecular Dynamics Simulations. J Am Chem Soc. 2011 May 4;133(17):6563-77.
 
Braun, A.R., Brandt, E., Edholm, O., Nagle, J.F., and Sachs, J.N. Determination of Electron Density Profiles and Area from Simulations of Undulating Membranes. Biophys J. 2011 May 4;100(9):2112-20.
 
Brandt, E., Braun, A.R., Sachs, J.N., Nagle, J.F., and Edholm, O. Interpretation of Fluctuation Spectra in Lipid Bilayer Simulations. Biophys J. 2011 May 4;100(9):2104-11.
 
Perlmutter, JD., Sachs, JN. Inhibiting Lateral Domain Formation in Lipid Bilayers: Simulations of Alternative Steroid Headgroup Chemistries. J. Am. Chem. Soc. 2009 131:16362–16363.
 
Perlmutter, JD., Sachs, JN. Experimental verification of lipid bilayer structure through multi-scale modeling. Biochim. Biophys. Acta, Biomembr. 2009 1788:2284-2990.
 
Perlmutter, JD., Braun, AR, and Sachs, JN. Curvature Dynamics of alpha-Synuclein Familial Parkinson’s Disease Mutants: Molecular Simulations of the Micelle-and Bilayer-Bound Forms. J. Biol. Chem. 2009 284: 7177-7189.
 
Kucerka, N., Perlmutter J., Pan J., Tristram-Nagle S., Katsaras J. and Sachs JN. The effect of cholesterol on short- and long-chain monounsaturated lipid bilayers as determined by molecular dynamics simulations and x-ray scattering. Biophys. J. 2008. 95:2792-2805.