Liphardt Lab Research
We're a biophysics lab. Broadly, we pursue two intersecting research directions: (I) exploration of biological spatial organization on the mesoscale (10 nm - 10 microns) and (II) characterization of the mechanics of normal and dysplastic cells and tissues.
Current projects include studies of the mechanobiology of tumor progression, super-resolution studies of protein clustering in membranes, and single-molecule studies of transport through biological pores and channels.
We also invent and refine tools for precision control and characterization of cells and tissues. Control technologies include light-powered proton pumps, which allow us to optically manipulate the proton-motive-force (pmf) within living cells. Characterization technologies include super-resolution light microscopy.
Our lab is located in Stanley Hall, very close to the Campanile.
Patterns, Energy and Information
Self-assembly of Chemotaxis Proteins in E. coli
In collaboration with Eric Betzig, Hari Shroff, and Ned Wingreen, we are using super-resolution light microscopy to investigate how certain proteins self-assemble into a variety of patterns in the cell membrane. Our overall goal is to relate biological spatial organization to aggregate cellular functions, such as reliable and efficient chemotaxis. The image shows a single E. coli cell expressing labeled Tar chemotaxis receptors. Each dot corresponds to one protein.
Mechanochemistry of the Nuclear Pore Complex
In collaboration with Karsten Weis, we are using single-molecule tracking approaches to learn how the NPC controls access to the nucleus. The image shows a schematic of a NPC in the nuclear membrane, and a single cargo transiting the pore. The panel on the right shows a single cargo being tracked as it translocates the pore.
New Tools for Measurement and Control
Plasmon Rulers: a new tool for measuring molecular distances
A key problem in biophysics is the measurement of nm scale distances. In collaboration with the lab of Paul Alivisatos, we have been using characterizing the distance dependence of the plasmon resonance between two gold (or silver) nanoparticles. Unlike conventional dyes, noble metal nanoparticles do not blink or bleach, making it possible to track them, or use them to measure distances, for arbitrary durations. For an overview of our ongoing plasmon resonance work, please see the meeting report in Science 308 (2005).
Optical control of cellular proton-motive-force
We synthesize light powered and controlled forms of the E. coli bacterium to help us understand the conversion of light into mechanical work in biological systems. The images below show a single E. coli cell that is stuck to a surface and that rotates when illuminated with green light. The cell uses the Proteorhodopsin light powered pump to harvest photons, creating a proton-motive-force, that in turn drives the flagellar motor.
Optical Trapping and Manipulation of Nanowires
Semiconductor nanowires have unique optical and electronic properties. We're collaborating with the lab of Peidong Yang to find new ways of manipulating nanowires, and assembling them in to 3-D heterostructures. Primarily, we use optical tweezers to grab nanowires and fuse them to other wires and objects.
Optical Force-Measuring Tools; Polymer Physics; Nucleic Acids
Mechanical properties of RNA
RNA molecules perform many activities in the cell, including structural scaffolding, information transfer (e.g. mRNA and tRNA), and catalysis (e.g. catalysis of the peptide bond during protein synthesis). We would like to learn how RNA folds, and characterize the mechanical properties of RNA, such as resistance to mechanical stresses and strains.
Forces inside DNA loops
Imagine grabbing a single piece of DNA and trying to bend it. What are the forces needed to do that? We use force sensors with optical readout to directly measure the forces inside small, highly strained DNA loops.
