AP242/MCB161: Introduction to Single-Molecule Biophysics

This course provides a practical introduction to single-molecule biophysics, a vibrant field that over the past several decades has transformed how we probe biological and soft-matter systems at the most fundamental level. We will build up the foundations of imaging science—including geometric and Fourier optics, light propagation and diffraction, resolution and transfer functions, noise and detectors, and the physics of fluorescence—before examining state-of-the-art single-molecule methods such as single-molecule FRET, single-molecule localization microscopy (SMLM), STED, MINFLUX, optical tweezers, and single-particle cryo-EM and tomography. Emphasis will be placed on how these technological advances have enabled key scientific insights in biology and soft-matter science, and on when and how single-molecule approaches can be effectively applied. Because final projects are based on topics chosen by the students, participants can chart an individualized path most beneficial to their own research, and are encouraged to explore cutting-edge directions such as the use of artificial intelligence, quantum single-molecule sensing, and other novel or cross-disciplinary approaches for advancing mechanistic understanding of biological and soft-matter systems.