One of the most important interactions in biotechnology is that between a biomolecule or biomolecular label and a surface in solution. These interactions affect binding and labeling efficiency in biosensors [1], the effectiveness of many "lab-on-a-chip" systems, and the use of biomolecules for self-assembly. We are working to develop a fundamental, multi-scale understanding of how biomolecules and labels interact with functionalized surfaces under laminar flow. Our program combines state-of-the-art micro-to-nanoscale modeling and computation with experimental studies of 3D and 2D molecular diffusion and binding of single biomolecules and labels at surfaces.
Experimentally, a custom optical nanoprobe has been developed based on total internal reflection fluorescence (TIRF) for observing fluorescent, biofunctionalized nanoparticles (semiconductor quantum dots) near a surface in flow in real time with single particle resolution. Videos at frame rates up to 57 frames/s show particles diffusing at the surface, binding both transiently and permanently to the surface, and translating in flow with velocities increasing with distance away from the surfaces. Analysis of the videos reveals interesting and surprising diffusive behavior as a function of surface chemistry and morphology and buffer composition.
Theoretically, we are investigating the dynamics of single- and double-stranded DNA near surfaces under flow using a new computational method for non-equilibrium biomolecular dynamics (Bio-NEMD) [2]. In addition to the structural changes of the free or immobilized DNA, many other dynamical properties have been investigated, including hydrodynamic force, bonding force, and DNA-DNA and DNA-solvent interactions. By extending the existing biomolecular equilibrium simulation software CHARMM to enable Bio-NEMD calculations, we have been able, for the first time, to directly calculate the DNA molecular relaxation time and the hydrodynamic forces on DNA molecules at the atomic level. Methods and algorithms developed in this work are also suitable for incorporation into larger and longer computations, e.g., of solvent transport or DNA hybridization.
1. Sheehan and Whitman, Nano Lett. 5 (2005) 803.
2. Wang and Sandberg, Nanotechnology 18 (2007) 135702.
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