Supramolecular Structures Lab
Tethered Bilayer Lipid Membranes (tBLMs) for Biomedical Research
Physiological bilayer membranes – fluid leaflets self-assembled by non-covalent interactions and a mere 5 nanometers thin – are ubiquitously used in biological cells but much to delicate to use in practical applications. While a great deal of fundamental research has been achieved with model systems such as "Black Lipid Membranes", i.e. freely suspended bilayers between two semi-infinite buffer compartments, these are entirely unsuitable if it comes to long-term experiments, be it systematic screening, observations over extended periods or technological applications. Also, such BLMs are not suitable for high-res structural investigations, because they're so small in lateral extension (~ 10-2 mm2).
Self-assembled lipid membranes may serve as functional interface architectures in applications that range from biosensorics to pharmacological screening.
Our workhorses: Neutron or x-ray reflection is used to characterize the molecular structure of tBLMs. Electrochemical characterization is used to assess their capacitance, residual conductance, and defect density. Fluorescence correlation spectroscopy (FCS) is a useful technique to study membrane dynamics and surface plasmon spectroscopy (SPR) quantifies the kinetics of protein or peptide binding to functionalized membranes.
We have developed specific molecular surface architectures, substrate-supported tethered bilayer lipid membranes (tBLMs), in which the 50 Å thick bilayer membrane is adsorbed to a solid surface via a hydrated chemical tether. Ingredients for this work are a dedicated synthetic chemistry (developed by David Vanderah, NIST-CSTL), an unconventional preparation protocol for bilayer completion (first introduced by the Cornell group), electrochemical impedance spectroscopy (the EIS technique has been brought to us by Gintaras Valincius of the Biochemistry Institute in Vilnius, Lithuania) for facile system optimization, and neutron reflectometry (NR) for the high-res structural assessment of the resulting architecture.
The result is an optimized experimental system, easy and reproducibly to prepare in simple bake-and-shake sample preps, that we use in various applications within a multitude of collaborations:
In all cases, the tBLMs permit us to explore dimensions in biomedical research that have not previously been accessible.
A collaborative platform for research
tBLM optimization at the NIST Center for Neutron Research. More...
Alzheimer's peptide amyloid β: Mechanisms of Aβ toxicity. More...
Initial steps of viral assembly studied in structural investigations of the HIV-1 gag protein at membrane surfaces. More ...
Membrane incorporation of the protein toxin pore α-hemolysin. More...