Real-Time Single-Cell Probing of the Spatiotemporal Regulation of Cancer Cell Chemotaxis Using Nano-Scale Biomedicaltechnologies

Chemotaxis of cancer cells in the surrounding microenvironment is an essential component of tumour dissemination during progression and metastasis. Chemotaxis is the result of three separate steps, including chemosensing, polarization and locomotion. A rigorous understanding of the mechanism of cancer cell chemotaxis will help us develop novel concepts and strategies for cancer therapy. Recently, concepts, principles and methods from the physical sciences have been applied to the cancer biology. This project will present an innovative approach on chemotaxis assay and provide a bottom-up approach to address cancer cell chemotaxis. On the one hand, we apply high-resolution optical tweezers system, together with microfluidic system with accurate sample temperature control, to conduct spatial and temporal regulation of chemotaxis, where optically trapped bead is coated with the chemoattractant EGF (epidermal growth factor). On the other hand, we further construct a single-cell platform as a means to examine cellular behaviour in response to chemoattractor. This project will primarily focus on three specific aims, including Aim 1: Spatiotemporal control of cell polarization during EGF chemotaxis; Aim 2: Investigating the relationship between polarized intracellular signals and the cytoskeletal dynamics, and Aim 3: Identifying and quantifying modes of locomotion during epidermal growth factor chemotaxis. We anticipate the proposed bottom-up approach based on nano-scale biomedicaltechnologies, together with the platform at single-cell level could be applied to build a quick screening method for detection and treatment evaluation of many types of cancer during chemotaxis.