Jonathan N. Sachs Assistant Professor 612/624-7158 email: jnsachs@umn.edu

• B.S., Mathematical Biochemistry, University of Michigan, 1996.
• Ph.D., Biomedical Engineering, Johns Hopkins University, 2003.
• NIH NRSA Postdoctoral Fellowship, Yale University, 3/04 - 8/06

Computational Molecular Modeling and Experimental 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.

Publications

Kucerka, K., Pencer, J., Sachs, JN., Nagle, JF. and Katsaras J. Curvature effect on the structure of phospholipid bilayers. Langmuir. 23 (3): 1292-1299 JAN 30 2007.  

Sachs, JN., Engelman, DM. Introduction to the Membrane Protein Reviews: The Interplay of Structure, Dynamics, and Environment in Membrane Protein Function Annu Rev Biochem. 2006.

Chin C, Sachs JN and Engelman DM. Transmembrane homodimerization of receptor-like protein tyrosine phosphatases. FEBS Lett. 579(17), 3855-8 2005

Nanda H, Sachs JN, Petrache HI, Woolf TB. Environmental effects on glycophorin A folding and structure examined through molecular simulations J. Chem. Theory and Comp. (3): 375-388 2005.

Sachs JN, Shen H, and Saltzman WM. Polymers for gene therapy in cancer: New approaches for specificity of expression. Gene Therapy 12 (12): 954-955 2005.

Sachs JN, Crozier PS and Woolf TB. Atomistic simulations of biologically realistic transmembrane potential gradients. J. Chem. Phys. 121 (22): 10847-10851 2004.

Sachs JN, Petrache HI, and Woolf TB. Changes in phosphatidylcholine headgroup tilt and water order induced by monovalent salt: molecular dynamics simulations. Biophys. J. 86; 3772-3782 2004.

Sachs JN, Woolf, TB Understanding the Hofmeister effect in interactions between chaotropic anions and lipid bilayers: Molecular dynamics simulations. J. Amer. Chem. Soc. 125 (29): 8742-8743 2003.

Sachs JN, Petrache HI, and Woolf TB. Interpretation of small angle X-ray measurements guided by molecular dynamics simulations of lipid bilayers. Chem. Phys. Lip. 126: 211-223 2003.

Sachs JN, Petrache HI, Zuckerman DM, and Woolf, TB. Molecular dynamics simulations of ionic concentration gradients across model bilayers. J. Chem. Phys. 118 (4): 1957-1969 2003.

Petrache HI, Zuckerman DM, Sachs JN, Killian JA, Koeppe RE II and Woolf, TB. Hydrophobic matching mechanism investigated by molecular dynamics simulations. Langmuir 18 (4): 1340-1351 2002 .

Grossfield, A., Sachs, J., and Woolf, TB. Dipole lattice membrane model for protein calculations. Proteins 41:211-223 2000.