Tumor angiogenesis is a key regulator of tumor growth and metastasis. Assays allowing the analysis of tumor angiogenesis are an essential tool to elucidate the role played by the tumor microenvironment in regulating tumor angiogenesis. The assays should also be capable of systematically investigating the effects of physiologically relevant, mechanical and chemical stimuli and their synergistic interactions. The high optical resolution of microfluidic assays facilitates three-dimensional studies of cellular morphogenesis. Their versatility can be applied to study the multi-parameter control of angiogenic factors.

Human tissues are sophisticated ensembles of various cell types embedded in the complex but defined structures of the extracellular matrix (ECM). ECM is configured in a hierarchical structure from nano- to microscale, with many biological molecules forming large scale configurations and textures with feature sizes up to macroscopic scale (several hundred microns). The physicochemical, biological and mechanostructural properties of native ECM play a critical role in constructing a microenvironment for cells and tissues. In conjunction with the rapid evolution of material science and its fabrication techniques, studies of the topography and elasticity of ECM and other materials have allowed advanced interrogation of cellular mechanotransduction and cellular responses to mechanostructural cues. By learning from and mimicking the highly organized ECM structures found in vivo, topography-guided approaches to regulate cell function and fate have been widely investigated in the last several decades. Here, we review recent efforts in mimicking the micro- and nanotopography of the native ECM in vitro for the regulation of cellular behaviors. We also discuss how these biomimetic topographical surfaces have been applied to fundamental cell mechanobiology studies into cell adhesions, migrations, and differentiation as well as toward efforts in tissue engineering.

Live cells can sense the mechanical characteristics of the microenvironment and translate the mechanical cues to intracellular biochemical signals in physiology and disease. To investigate intracellular signaling transduction during mechanosensing, nanotechnologies, and FRET live-cell imaging technologies have been developed to visualize the output signals in real time, such as intracellular molecular activity. Meanwhile, micropatterned technologies have been applied to modulate the physical and mechanical environment surrounding the cell to fine-tune the input signals in cellular mechanosensing. These advanced technologies can join forces and shed new light into the molecular networks that control mechanotransduction in normal conditions and disease.