Design of Fiber Networks for Studying Metastatic Invasion

Cancer metastasis, the dissemination of cancer cells from the primary tumor site to distal organs in the body, is one of the leading causes of cancer-related deaths globally. It is now appreciated that metastatic cells take advantage of specific features of surrounding fibrous extracellular matrix that favors invasion. However, the exact contributions of the role of fiber feature size, orientation, and organization remain only partially described. Here using non-electrospinning Spinneret based Tunable Engineered Parameters (STEP) fiber platform, we detail our quantitative findings over the past decade on cancer cell behavior in environments of controlled fiber dimensions, orientation, and hierarchy that can mimic essential features of native ECM. We present a biophysical model of invasion along aligned fibers that starts with cells forming protrusions followed by invasion of cells from a monolayer in single, multi-cell chain and collective modes. Using a mismatch of fiber diameters, we describe a new method to protrutype single protrusions and describe migratory behavior of cells in different shapes. Altogether, control over fiber geometry and network architecture enables the STEP platform to unlock a new paradigm in the interrogation of the fundamental biophysical mechanisms underlying the migratory journey of cells during cancer metastasis.