Biochemistry and Molecular Biology
Penn State Science
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Paul Cremer

Paul Cremer

Main Content

  • Professor of Chemistry and
  • Professor of Biochemistry and Molecular Biology
  • J. Lloyd Huck Chair in Natural Sciences
212 South Frear
(mailbox 104 Chemistry)
University Park, PA 16802
Email: psc11@psu.edu

Research Interests

Multidisciplinary field of biological surface and interface science

Graduate Programs

BMMB, CHEM

Research Summary

Our research group works in the multidisciplinary field of biological surface and interface science. We have made contributions in bioanalytical as well as biophysical chemistry. This involves the development and exploitation of high throughput microfluidic devices, which allows us to obtain large quantities of thermodynamic information on protein folding, protein-membrane binding, hydrophobic collapse, and two-dimensional lipid diffusion. In the age of proteomics, it would be imposible to obtain enough data or make use of the small sample sizes available without exploiting microfluidics. These thermodynamic data are then compared with molecular level information taken by atomic force microscopy, sum frequency generation, ATR-FTIR, surface enhanced Raman spectroscopy, fluorescence quenching, and NMR to elucidate the molecule level details of biointerfacial processes.

One very significant contribution from our group has been in the field of interfacial water structure and ion-macromolecule interactions (the Hofmeister Effect).  Our studies demonstrated that direct interactions between proteins and ions dominate the physical properties of electrolyte solutions. This work helped revise the century old theory that such interactions were indirect and involved mostly ion-bulk water interactions. In other words, the key to ion specificity is understanding interactions at the protein/water interface. We have also elucidated the molecular level details for the interactions of osmolytes, small uncharged molecules, with proteins. Most osmolytes help stabilize protein structure, but the mechanism has been unknown. We were able to demonstrate that trimethylamine N-oxide, a powerful stabilizer of native structure, adopts an unusual conformation at the air/water and oil/water interfaces such that the methyl groups of the molecule point down into the solution and the oxide moiety faces upward toward the more hydrophobic medium. This orientation appears to be the result of the electric fields at hydrophobic/water interfaces that orients the molecule‚Äôs dipole. This unusal orientation should help lead to hydrophobic collapse at the protein/water interface and, hence, protein stabilization. We have also been able to show that urea helps denature proteins through interfacial accumulation that involves preferential hydrophobic interactions rather than hydrogen bonding affects.

We have also made breakthroughs in understanding ligand-receptor binding mechanisms at fluid biomembrane interfaces.  This work demonstrated that ligand density and surface presentation within a lipid bilayer can enhance or attenuate equilibrium dissociation constants by 4 orders of magnitude.  Two-dimensional ligand-ligand interactions at the surface play a crucial role in this process. Our work has also led to a clearer understanding of protein displacement on implant surfaces (the Vroman Effect).  We have also designed several new analytical techniques such as on-chip binding constant measurements for multivalent ligand-receptor binding, temperature gradient microfluidics, and local pH modulation for label-free biosensing. The latter exceeds the sensitivity of SPR and is subject to less problems from biofouling. Most recently, we have shown that a new fluorescence quenching assay can be developed to assay small drug-like molecules and ions interacting with lipid membranes, which is crucial to pharmecutical development.