Probing molecular forces with high-throughput single-molecule manipulation
Boston Children's Hospital/Harvard Medical School
Cellular and Molecular Medicine/Biological Chemistry & Molecular Pharmacology and Pediatrics
From governing the immune response, to determining cell fate and tissue development, mechanical forces play key regulatory roles throughout biology. This emergent field of "mechanobiology" is leading to new insights into diseases such as bleeding disorders, cancer, infectious diseases, osteoporosis and asthma, and inspiring new approaches for treatment. Technological developments that enable the precise manipulation of single molecules and cells have been a driving force in the development of the field. However, growth of the field is impeded by current technology as it can be expensive, technically challenging, and low-throughput. To meet this challenge, we will develop an approach that we call "single-molecule centrifugation”, which will enable researchers to perform massively parallel single-molecule force manipulation in a simple and inexpensive way. By incorporating a miniature microscope into a centrifuge (an instrument we call the Centrifuge Force Microscope), researchers will be able to apply forces to thousands of individual molecules at once while observing their response, enabling such measurements to be made thousands of times faster than traditional approaches, for a fraction of the cost. This approach has the potential to revolutionize many areas of biomedical research, from biochemistry to structural biology, by accelerating new discoveries and enabling these previously slow, expensive, and highly technical single-molecule methods to be performed by almost anyone.