Study of Cell & Single Molecule Biomechanics

As the basic unit of life, the cell is a biologically complex system. It requires a combination of various approaches including biomechanics in order to understand the cell. With the recent progress in cell and molecular biology, the field of cell mechanics has grown rapidly over the last few years. This research investigates the response of cells to mechanical forces in a quantitative manner and the biomechanics and kinetics of cell adhesion (eg. cell-cell or cell-substrate interactions) at the cellular as well as molecular levels. Such studies are useful in understanding how a diseased cell can differ from that of a normal cell by subjecting them to mechanical forces and why cells tend to adhere better to certain biomaterials as compared to others.

Recent developments of optical and mechanical probes that are sensitive enough to make measurements on single biological molecules have ushered in a new era of biomechanical studies. Not only can we do such measurements and be able to characterize molecules, we can also investigate the properties of molecules whose roles and functions are yet unknown. Our goal in biomolecular mechanics is to be able to mechanically characterize the behaviour of single molecules. Ultimately, we hope to address questions such as: How does a biomolecule, eg. a protein, respond to an applied force? How does it move, fold and unfold? Biomolecules that is of interest include DNA, proteins and cytoskeletal structures.

Figure 1: Optical trap method to study cell and single molecule mechanics

In order to obtain quantitative measurements of forces and deformation experienced by cells and biomolecules, techniques such as optical trapping, atomic force microscopy and micromanipulation will be used. The optical trapping method employs the refraction of laser light. When laser light is passed through transparent objects, it gets refracted in such a way that there is always more light pressure pushing the object towards the focal point than there is pushing it away from it. These forces or radiation pressures arise from the momentum of the light itself. Figure 1 shows how a cell or a DNA strand can be stretched using the laser tweezers. Two transparent microsized beads are attached diametrically across the cell. For the DNA strand, the beads are attached at its two ends. The optical or laser tweezers are then used to trap the two beads and move them apart. The response of the cell and DNA to the stretching force can then be studied.

Another technique used in studying the biomechanics of single molecules is to employ atomic force microscopy (AFM). The biomolecule, eg. a protein can have one of its ends attached to the cantilever tip and the other end attached to a substrate (Figure 2). As the tip moves upwards, the variation of stretching force with deformation of the biomolecule can thus be quantitatively assessed.

A major part of this research is conducted at the Nano/Micro Mechanics Lab (http://www.bioeng.nus.edu.sg/nanolab/nanolab.html), Division of Bioengineering which houses the multimode AFM system, optical tweezers, laser scissors and micromanipulators. Our collaborators include Prof TM Lim (Department of Biological Sciences), Prof S Ramakrishna (Biomaterials Lab), Dr CH Sow (Department of Physics), Dr HQ Mao (Johns Hopkins Singapore), Dr S Valiyaveettil (Department of Chemistry) and Dr Shu Wang (IMRE).