个人简介

Postdoctoral Fellow, University of Oxford - 2008, PhD, Texas A&M University – 2004, BS in Chemistry, University of Florida - 1999

研究领域

Cell membrane mimics/membrane transport studies/functional bionetworks

We reconstruct cell membranes from natural and synthetic molecular components. These lipid bilayers provide a general bio-architecture that can be precisely tuned to study a variety of biological problems. We focus on the study of ion channels, transporters and other membrane-penetrating species. In addition, bilayer networks enable the creation of biological mimics whose functions are based on the type of membrane proteins incorporated into the network. 1. Bionetworks Droplets immersed in an oil/lipid mixture become encased in a lipid monolayer. When two such droplets are contacted, a droplet-interface bilayer (DIB) is formed; many connected droplets comprise a bionetwork. By incorporating membrane proteins such as ion channels and pumps into DIBs, bionetworks can be engineered to carry out specific functions. Using this approach, we build stimulus responsive bionetworks in order to model electrically driven systems such as heart and nerve tissues. 2. Membrane Transport The trafficking of molecules across cell membranes is of central interest in metabolism and disease. Assays of membrane transport using live cells are performed under stringent conditions in order to maintain cell viability. Using arrays of DIBs, we study the transport of molecules from one droplet to another, maintaining the conservation of mass throughout the assay. Both passive transport (diffusion of molecules across the bilayer) and active transport (membrane transporters using energy to drive transport) are investigated. 3. Single Ion Channel Investigation The incorporation of functional ion channels into artificially formed lipid bilayers is a challenging task. Many species of ion channel are delicate and quickly denature or otherwise lose activity when purified from their native systems. Using a mechanical probe, we transfer membrane proteins (such as ion channels) directly from cellular systems to preformed bilayers for single-channel investigation by electrophysiology. Automation of the transfer technique represents a key advancement in the study of ion channels.

近期论文

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Leptihn, S.; Castell, O. K.; Cronin, B.; Lee, E.-H.; Gross, L. C. M.; Marshall, D. P.; Thompson, J. R.; Holden, M.; Wallace, M. I. Constructing droplet interface bilayers from the contact of aqueous droplets in oil. Nat Protoc 2013, 8, 1048–1057. PDF Lein, M.; Huang, J.; Holden, M. A. Robust reagent addition and perfusion strategies for droplet-interface bilayers. Lab Chip 2013, 13, 2749–2753. PDF Fischer, A.; Holden, M. A.; Pentelute, B. L.; Collier, R. J. Ultrasensitive detection of protein translocated through toxin pores in droplet-interface bilayers. Proc. Natl. Acad. Sci. U.S.A. 2011, 108, 16577–16581.PDF Huang, J.; Lein, M.; Gunderson, C.; Holden, M. A. Direct quantitation of peptide-mediated protein transport across a droplet-interface bilayer. J. Am. Chem. Soc. 2011, 133, 15818–15821. PDF Maglia, G.; Heron, A. J.; Hwang, W. L.; Holden, M. A.; Mikhailova, E.; Li, Q.; Cheley, S.; Bayley, H. Droplet networks with incorporated protein diodes show collective properties. Nat Nanotechnol 2009, 4, 437–440. PDF Syeda, R.; Holden, M. A.; Hwang, W. L.; Bayley, H. Screening blockers against a potassium channel with a droplet interface bilayer array. J. Am. Chem. Soc. 2008, 130, 15543–15548. PDF Hwang, W. L.; Chen, M.; Cronin, B.; Holden, M. A.; Bayley, H. Asymmetric droplet interface bilayers. J. Am. Chem. Soc. 2008, 130, 5878–5879. PDF, Supporting Info Hwang, W. L.; Holden, M. A.; White, S.; Bayley, H. Electrical behavior of droplet interface bilayer networks: experimental analysis and modeling. J. Am. Chem. Soc. 2007, 129, 11854–11864. PDF, Supporting Info *Holden, M. A.; Needham, D.; Bayley, H. Functional bionetworks from nanoliter water droplets. J. Am. Chem. Soc. 2007, 129, 8650–8655. PDF, Supporting Info See also: Nature Highlight, Scientific American, Analytical Chemistry - Lab Fab *Holden, M. A.; Jayasinghe, L.; Daltrop, O.; Mason, A.; Bayley, H. Direct transfer of membrane proteins from bacteria to planar bilayers for rapid screening by single-channel recording. Nat. Chem. Biol. 2006, 2, 314–318. PDF See also: News and Views Nature Chemical Biology PDF Jung, S. Y.; Holden, M. A.; Cremer, P. S.; Collier, C. P., Two-component membrane lithography via lipid backfilling. ChemPhysChem 2005, 6, 423-426. PDF Holden, M. A.; Cremer, P. S. Microfluidic tools for studying the specific binding, adsorption, and displacement of proteins at interfaces. Annu Rev Phys Chem 2005, 56, 369–387.PDF *Holden, M. A.; Bayley, H. Direct introduction of single protein channels and pores into lipid bilayers. J. Am. Chem. Soc. 2005, 127, 6502–6503. PDF, Supporting Info Kataoka, S.; Gurau, M. C.; Albertorio, F.; Holden, M. A.; Lim, S. M.; Yang, R. D.; Cremer, P. S. Investigation of water structure at the TiO2/aqueous interface. Langmuir 2004, 20, 1662-1666. PDF Holden, M. A.; Jung, S. Y.; Yang, T. L.; Castellana, E. T.; Cremer, P. S. Creating fluid and air-stable solid supported lipid bilayers. J. Am. Chem. Soc. 2004, 126, 6512-6513. PDF Holden, M. A.; Jung, S. Y.; Cremer, P. S. Patterning enzymes inside microfluidic channels via photoattachment chemistry. Anal. Chem. 2004, 76, 1838-1843. PDF Yang, T. L.; Baryshnikova, O. K.; Mao, H. B.; Holden, M. A.; Cremer, P. S. Investigations of bivalent antibodies binding on fluid planar supported phospholipid membranes: The effect of hapten density. J. Am. Chem. Soc. 2003, 125, 4779-4784. PDF Jung, S. Y.; Lim, S. M.; Albertorio, F.; Kim, G.; Gurau, M. C.; Yang, R. D.; Holden, M. A.; Cremer, P. S. The Vroman effect: A molecular level description of fibrinogen displacement. J. Am. Chem. Soc. 2003, 125, 12782-12786. PDF Holden, M. A.; Kumar, S.; Castellana, E. T.; Beskok, A.; Cremer, P. S. Generating fixed concentration arrays in a microfluidic device. Sensors and Actuators B 2003, 92, 199-207. PDF Holden, M. A.; Kumar, S.; Beskok, A.; Cremer, P. S. Microfluidic diffusion diluter: bulging of PDMS microchannels under pressure-driven flow. J. Micromech. Microeng. 2003, 13, 412-418. PDF Holden, M. A.; Cremer, P. S. Light activated patterning of dye-labeled molecules on surfaces. J. Am. Chem. Soc. 2003, 125, 8074-8075. PDF Mao, H. B.; Holden, M. A.; You, M.; Cremer, P. S. Reusable platforms for high-throughput on-chip temperature gradient assays. Anal. Chem. 2002, 74, 5071-5075. PDF