Mechanotransduction – the process of converting mechanical forces into immediate biochemical changes or distal changes in cell fate – is now an appreciated facet of biology. Many proteins, particularly those in fibrous extracellular and intracellular networks participate in load bearing and mechanotransduction, and recent work has highlighted how the fibrous nature of these networks is key in relaying mechanical signals to cells. What if the proteins that compose the extracellular matrix or the intracellular cytoskeleton are themselves mechanotransducers by, e.g., directly revealing ‘cryptic’ enzymatic activity? How might changes in cell mechanics modify fundamental cellular processes like nuclear transport, in addition to cell fate? In this talk, I will present our work using in situ advanced microscopy to quantify protein structure in fibrous protein biomaterials in situ under different mechanical loads. I will also show how changes in cell and tissue mechanics, as seen in many solid tumors, can modify nuclear transport of chemotherapy and (time bearing) can be used as a biomarker to subtly identify tumor cells using a mechano-molecular flow cytometer. Long term, we aim to understand how mechanics influences physiology from the biophysics of protein networks to essential cellular functions.