Force plays an essential role in many biological systems at different length. Physical forces, together with chemical signals contribute to the proper functioning of various biological processes. For example, cells sense and transduce environmental physical cues into biochemical signals so as to realize different cellular processes, such as proliferation, migration. and apoptosis. Thus elucidating the details of force involved in various biological systems is thus crucial for a complete understanding of their biological mechanisms such as biomolecule's mechanical properties, dynamic conformations, native structure, and cell's physical properties. The ability of probing and studying the forces in biology has been revolutionized over the past two decades. Atomic force microscopy (AFM), for example, has been proven a powerful technique in measuring forces in piconewton range, relevant in biological scales.

In this thesis, I explored the AFM application on different biological systems ranging from single molecule level to single cell level. In the first part, I will show that single molecule manipulation by AFM can reveal the mechanical properties, equilibrium states, and dynamic conformations of proteins and nucleic acids. In the second part, I will extend the application of AFM on single cells and show that the cancer cells adaption to microenvironment can be revealed by force signatures. In addition, I will also demonstrate the investigation of invasiveness of cancer cells via a specific cell line using AFM force studies. Finally, I will discuss future outlooks of AFM cell studies.