Biological signaling processes are comprised of diverse molecular species which present a number of chemical and physical challenges with respect to chemical measurement. The most challenging species to measure, and thus the ones whose roles are least defined in signaling pathways are those compounds that lack inherent chemical moieties that are amenable to high sensitivity spectroscopic or electrochemical detection. The majority of our research efforts are focused on the development of biomimetic and biofunctionalized sensor strategies that allow detection of key signaling components, while also proving useful for other key bioanalyses including drug discovery and clinical diagnostics.
Biomimetic platforms provide key advantages for chemical analysis in complex systems. Nearly all molecular species interact, at some level, with soluble and/or membrane proteins. While the scientific endeavor has spent the last 200+ years developing approaches to quantify chemical species, eons of natural selection has provided highly efficient biological recognition events, particularly for compounds that interact with transmembrane proteins (TMP). Our primary research focuses on integrating these naturally occurring interactions, or closely related synthetic mimics, into platforms that are conducive for measurement of biomolecular species with unprecedented selectivity, and sufficient sensitivity and temporal and spatial resolution to elucidate the molecular composition of key biological functions. Specifically, we are interested in integrating TMPs and other proteins into measurement platforms. TMPs regulate a multitude of biological functions by transducing information from the extracellular domain to the intracellular domain upon ligand binding. Furthermore, the broad diversity and number of TMPs coupled with the chemical diversity of corresponding ligands present a key opportunity for chemical measurements if a number of key challenges can be overcome.
|Figure 1. Schematic representation of four major research thrusts in the Aspinwall group. We have developed a range of next-generation sensing platforms that enable integration of biological transducers, including membrane proteins. A key element of each measurement strategy is the integration of stabilized membranes into which ion channels and/or receptors can be integrated in a functional manner. During the course of our research, we have overcome a number of key limitations in the integration of proteins, particularly TMPs, into sensing platforms, including issues of fundamental molecular compatibility and stability of biological membranes with inorganic sensor matrices.|
Ross, E.E.; Mansfield, E.; Huang, Y.; Aspinwall, C.A. "In situ Fabrication of 3-Dimensional Chemical Patterns in Fused Silica Separation Capillaries with Polymerized Phospholipids." J. Am. Chem. Soc. 127: 16756-7, 2005.
Hapuarchchi, S.; Premeau, S.; Aspinwall, C.A. "High Speed Capillary Zone Electrophoresis with Online Photolytic Optical Injection." Anal. Chem. 78: 3674-3680, 2006.
Cheng, Z.; D'Ambruoso, G.D.; Aspinwall, C.A. "Stabilized Porous Phospholipid Nanoshells" Langmuir 22: 9507-9511, 2006.
Mansfield, E.; Ross, E.E.; Aspinwall, C.A. "Preparation and Characterization of Cross-linked Phospholipid Bilayer Capillary Coatings for Protein Separations" Anal. Chem. 79: 3135-3141, 2007.
Bränström, R.; Leibiger, I.B.; Leibiger, B.; Aspinwall, C.A.; Corkey, B.E.; Berggren, P-O.; Larsson, O. "Single Residue (K332A) Substitution in Kir6.2 Abolishes the Stimulatory Effect of Long-Chain Acyl-CoA Ester: Indications for a Long-Chain Acyl-CoA Ester Binding Motif" Diabetologia, 50: 1670-1677, 2007.
Senarath-Yapa, M.D.; Phimphivong, S.; Coym, J.W.; Wirth, M.J.; Aspinwall, C.A.; Saavedra, S.S. "Preparation and characterization of poly(lipid) coated, fluorophore doped silica nanoparticles for cellular imaging" Langmuir, 23: 12624-12633, 2007.
Heitz, B.A.; Xu, J.; Hall, H.K., Jr.; Aspinwall, C.A.Saavedra, S.S. "Enhanced long-term stability for single ion channel recordings using suspended poly(lipid) bilayers." J. Am. Chem. Soc., 131: 6662-6663, 2009.
Heitz, B.A.; Jones I.W.; Hall, H.K. Jr.; Aspinwall, C.A. Saavedra, S.S. "Fractional polymerization of a suspended planar bilayer creates a fluid, highly stable membrane for ion channel recordings." J. Am. Chem. Soc. 132: 7086-7093, 2010.
Muhandiramlage, T.P.; Cheng, Z.L.; Roberts, D.L.; Keogh, J.P.; Hall Jr.,H.K.; Aspinwall, C.A. "Determination of pore sizes and relative porosity in porous nanoshell architectures using dextran retention with single monomer resolution and proton permeation." Anal. Chem., 84: 975-9761, 2012.
Berglund, E.; Berglund, D.; Akcakaya, P.; Ghaderi, M.; Dare, E.; Berggren, P.-O.; Kohler, M.; Aspinwall, C.A.; Liu, W.-O.; Zedenius, J.; Larsson, C.; Branstrom, R. "Evidence for Calcium-Regulated ATP Release in Gastrointestinal Stromal Tumors" Exp. Cell Res., 319:1229-1238, 2013.
Bright, L.K.; Baker, C.A.; Agasid, M.T.; Ma, L.; Aspinwall, C.A. "Decreased aperture surface energy enhances electrical, mechanical, and temporal stability of suspended lipid membranes." ACS Appl. Mater. Interfaces 5: 11918-11926, 2013.
Baker, C.A.; Bright, L.K.; Aspinwall, C.A. "Photolithographic fabrication of microapertures with well-defined, three-dimensional geometries for suspended lipid membrane studies." Anal. Chem. 85: 9078-9086, 2013.
Cheng, Z.L.; Al Zaki, A.; Jones, I.W.; Hall, Jr. H.K.; Aspinwall, C.A.; Tsourkas, A. "Stabilized porous liposomes with encapsulated Gd-labeled dextran as highly efficient MRI contrast agents" Chem. Comm., 50: 2502-2504, 2014.
Li, Z; Muhandiramlage, T.P.; Keogh, J.P.; Hall, Jr., H.K.; Aspinwall, C.A. "Aptamer-functionalized porous phospholipid nanoshells for direct measurement of Hg2+ in urine" in press Anal. Bioanal. Chem., 2014.
Johnson, G.M; Chozinski, T.J.; Gallagher, E.S.; Aspinwall, C.A.; Miranda, K.M. "Glutathione Sulfinamide Serves as a Selective, Endogenous Biomarker for Nitroxyl Following Exposure to Therapeutic Levels of Donors" in press Free Radicals in Biology and Medicine, 2014.