Research in the Cremer lab involves the interplay of physical chemistry, biological chemistry, nanomaterials, and sensor design. Our group has developed high throughput, low sample volume techniques to study biophysical and bioanalytical problems that would otherwise be very difficult to tackle. This approach of integrating lab-on-a-chip and nanomaterial platforms with molecular level studies of biological interfaces is illustrated by the figure below. On the analytical side, our group has developed temperature gradient microfluidics, optical methods for interfacial patterning of biomolecules onto surfaces, nanoscale protein filter designs, air-stable supported phospholipid membranes, and evaporation templating. These methods have been exploited to study ligand-receptor binding on lipid membrane surfaces, protein adsorption, and the interactions of ions with proteins and membranes.
Figure: Microfluidic and array based platforms have been designed in the Cremer laboratory (upper left) for use in high-throughput, low sample volume assays. These techniques have been exploited in obtaining the molecular level details for ligand-receptor binding, protein biofouling, and polymer/protein folding.
Currently, we are working on a next generation of biosensors to that don't require a fluorophore or any other label. Such "label-free" assays consist, for example, of thin nanoparticle films, nanopores for measuring tiny currents, and pH modulation assays. We are also developing chemistry that will allow transmembrane proteins to be purified, isolated, and characterized on-chip in a fluid lipid bilayer without denaturation. Finally, we are unraveling the mechanism by which osmolytes such as urea denature proteins.
"The Molecular Mechanisms of Ion-Specific Effects on Proteins" Kelvin B. Rembert, Jana Peterova, Jan Heyda, Christian Hilty, Pavel Jungwirth, and Paul S. Cremer J. Am. Chem. Soc (2012) In press
"Phosphatidylserine Reversibly Binds Cu2+ with Extremely High Affinity" Christopher F. Monson, Xiao Cong, Aaron Robison, Hudson P. Pace, Chunming Liu, Matthew F. Poyton, and Paul S. Cremer J. Am. Chem. Soc 134 (2012) 7773-7779
"The Methyl Groups of Trimethylamine N-Oxide (TMAO) Orient Away from Hydrophobic Interfaces" Laura B. Sagle, Katherine Cimatu, Vladislav A. Litosh, Yi Liu, Sarah C. Flores, Xin Chen, Bin Yu, and Paul S. Cremer J. Am. Chem. Soc. 133 (2011) 18707-18712
"Chemistry of Hofmeister Anions and Osmolytes" Yanjie Zhang and Paul S. Cremer Ann. Rev. Phys. Chem. 61 (2010) 63-83
"Hydrogen Bonding of β-Turn Structure is Stabilized in D2O" Younhee Cho, Laura B. Sagle, Satoshi Iimura, Yanjie Zhang, Jaibir Kherb, Ashutosh Chilkoti, J. Martin Scholtz, and Paul S. Cremer J. Am. Chem. Soc. 131 (2009) 15188-15193
"The Inverse and Direct Hofmeister Series for Lysozyme" Yanjie Zhang and Paul S. Cremer PNAS 106 (2009) 15249-15253
"Investigating the Hydrogen Bonding Model of Urea Denaturation" Laura B. Sagle, Yanjie Zhang, Vladislav A. Litosh, Xin Chen, Younhee Cho, and Paul S. Cremer J. Am. Chem. Soc. 131 (2009) 9304-9310
"Detecting Protein-Ligand Binding on Supported Bilayers by Local pH Modulation" Hyunsook Jung, Aaron D. Robison, and Paul S. Cremer J. Am. Chem. Soc. 131 (2009) 1006-1014