Contact info:
Lawrence Berkeley National Laboratory
Physical Biosciences Division
One Cyclotron Road, MS Evans Hall
Berkeley, California 94720-1460
USA

Location: 481 Evans Hall
Email: fletch(at)uclink.berkeley.edu
Telephone: (510) 643-5624
Fax: (510) 642-5835
Fletcher Lab website: http://fletchlab.berkeley.edu/people.htm

Research Emphasis
The Fletcher Lab is developing a toolbox of new instruments and techniques – optical, mechanical, fluidic – that let us explore the “design rules” of cells and their molecular components. By learning how cells are built to physically interact with their environment, we aim to understand the operation of molecular machines that drive cell movements, identify physical mechanisms of disease, and develop medical devices for diagnosis and intervention of current health problems. In the future, the tools that help us understand how cells are engineered will also help us re-engineer cell function to address modern technology needs.

Optical & force microscopy: Optical microscopy has been and remains the primary method for studying the molecular organization and dynamics of living cells. However, pictures must be coupled with biophysical measurements to fully explain processes such as cell motility, cytokinesis, and phagocytosis. Analysis of cell and molecular mechanics requires spatial resolution on the scale of nanometers, force resolution below a nanonewton, and temporal resolution and range from milliseconds to hours. We are developing instruments based on the atomic force microscope (AFM) that combine the capabilities of force microscopy with advantages of optical imaging.

Molecular mechanics: Cells have been described as a collection of protein machines. Highly regulated conformational changes in proteins driven by nucleoside triphosphate hydrolysis, ion gradients, or other energy sources control the complex series of reactions that enable all cell functions. The cytoskeletal protein actin exerts forces necessary for a wide range of cell movements by assembling non-covalent polymers in the form of single filaments, stabilized bundles, and cross-linked meshes. We are studying the mechanical properties of actin and force generation by actin polymerization to understand the operation of this ubiquitous actuator.

Cell mechanics & disease: Mechanical properties of cells arise from the dynamic behavior of the cytoskeleton and physical interactions with the environment. Properties such as cell stiffness and adhesion play a vital role in normal physiological function. These and other properties can be disrupted by the onset of disease and may even contribute to the progression of disease. We are developing measurement techniques to quantify the role of mechanical properties in complications associated with cancer and pathogen infection.

Medical devices: Medical devices utilize innovations in technology and advancements in biology to improve diagnosis and treatment of disease. We are developing devices to solve medical problems related to cell and tissue mechanics. Effective delivery of therapeutic drugs into the bloodstream is essential for the treatment of many medical problems. As pharmaceutical companies develop more complex macromolecules for gene therapy, enzyme replacement, and disease immunization, conventional drug delivery techniques will no longer be sufficient. We are developing a new tool for controlled delivery of drugs in the body based on a high-speed liquid microjet.

Publications