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.

Dynamic mechanical forces play a critical role in modulating cellular function, and inclusion of these extracellular stimuli in culture systems may improve the relevance and utility of biological results. In this work, we discuss recent advances made by our research group in applying dynamically controlled mechanical stimuli to cells cultured in 2-D and 3-D arrayed environments. Advantages in throughput and precision arising from microengineering such systems are demonstrated, with illustrative examples of potential biological applications. Engineering challenges associated with building these culture systems are explored, and the design and fabrication strategies that we have developed are discussed. Finally, the ability to incorporate additional sensing technologies into these dynamic screening platforms is explored.

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.

The migratory ability of various cell types contributes to cell functions, physiological processes, and disease pathologies. Among the diverse environmental guiding mechanisms for cell migration, the electric field is a long-known important guiding cue. The electric field–directed cell migration, termed “electrotaxis,” can mediate processes that are important for human health such as wound healing, immune responses, and cancer metastasis. The growing interest in better understanding electrotaxis has motivated technological developments to enable more advanced electrotaxis studies. In particular, various microengineered devices have been developed and applied to studying electrotaxis over recent years. In general these new experimental tools can better control electric field application in cell migration experiments, whereas each developed tool offers its own features. Successful applications of the new devices have been demonstrated for studying electrotaxis of various cell types such as cancer cells, lymphocytes, animal models, and tissue cells related to wound healing, as well as for investigating electric field–mediated orientation responses in stem cells and yeast cells. In this chapter, we will provide the background information in directed cell migration, electrotaxis, and cell migration assays. We follow with a survey of fabrication and assembly methods of various microengineered electrotaxis devices and experimental setup and analysis methods, as well as their applications for cell studies. Finally, we conclude the chapter with our perspective on the issues challenging this research area and on the proposed directions for future development.

It has become increasingly appreciated that living mammalian cells are not just complex biochemical reactors but also sophisticated biomechanical systems that can adapt their mechanical properties to various signals and perturbations from the extracellular space, and integrate with intracellular signaling events through a process called mechanotransduction, to regulate cell behaviors. To gain fundamental insights into such biomechanical nature of mammalian cells, many biomechanical tools have been developed with unprecedented spatiotemporal resolutions covering both molecular and cellular length scales. In this chapter, we describe a recently developed biomechanical tool, termed “stretchable micropost array cytometry” (SMAC), which is capable of quantitative control and real-time measurements of both mechanical stimuli and cellular biomechanical responses with a high spatiotemporal subcellular resolution. We further discuss implementations of the SMAC for characterizing cell cytoskeletal contractile force, cell stiffness, and cell adhesion signaling and dynamics at both whole-cell and subcellular scales in real time. We conclude with remarks regarding future improvements and applications of the SMAC for cell mechanics and mechanobiology studies.

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.