Matthew A. Holden

Assistant Professor of Chemistry, University of Massachusetts

Contact Matthew Holden
Lab Group Home Page

Ph.D.: Texas A & M, 2004
Postdoctoral Training: Oxford University

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.

Selected Publications

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.
Lein, M.; Huang, J.; Holden, M. A. Robust reagent addition and perfusion strategies for droplet-interface bilayers. Lab Chip 2013, 13, 2749–2753.
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.
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.
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.
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.

Hwang, W. L.; Chen, M.; Cronin, B.; Holden, M. A.; Bayley, H., Asymmetric droplet interface bilayers. Journal of the American Chemical Society 2008, 130, (18), 5878-5879.

Holden, M. A.; Needham, D.; Bayley, H., Functional bionetworks from nanoliter water droplets. Journal of the American Chemical Society 2007, 129, (27), 8650-8655.

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. Nature Chemical Biology 2006, 2, (6), 314-318.

Jung, S. Y.; Holden, M. A.; Cremer, P. S.; Collier, C. P., Two-component membrane lithography via lipid backfilling. Chemphyschem 2005, 6, (3), 423-426.

Holden, M. A.; Cremer, P. S., Microfluidic tools for studying the specific binding, adsorption, and displacement of proteins at interfaces. Annual Review of Physical Chemistry 2005, 56, 369-387.

Holden, M. A.; Bayley, H., Direct introduction of single protein channels and pores into lipid bilayers. Journal of the American Chemical Society 2005, 127, (18), 6502-6503.

Holden, M. A.; Jung, S. Y.; Yang, T. L.; Castellana, E. T.; Cremer, P. S., Creating fluid and air-stable solid supported lipid bilayers. Journal of the American Chemical Society 2004, 126, (21), 6512-6513.

Holden, M. A.; Jung, S. Y.; Cremer, P. S., Patterning enzymes inside microfluidic channels via photoattachment chemistry. Analytical Chemistry 2004, 76, (7), 1838-1843.

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-Chemical 2003, 92, (1-2), 199-207.

Holden, M. A.; Cremer, P. S., Light activated patterning of dye-labeled molecules on surfaces. Journal of the American Chemical Society 2003, 125, (27), 8074-8075.