This project will develop and use biomaterials to investigate the effects of interstitial flow on cell behavior. The behavior of living cells in all organisms is influenced by a variety of factors in their surrounding tissue environment. Examples of these factors include the slow fluid flux outside cells, the confinement from neighbor cells or other components, and the rigidity of the tissue. This program will design and use new biomaterials to reveal the effects of environmental stimuli on important cell characteristics. To understand the mechanisms underlying cellular behavior, it is desired to employ an experimental model that provides a tissue-mimetic environment and allows for independent control of relevant contributing factors such as pore size. This remains a challenge for traditional biomaterial cell culture models which have been made of a single hydrogel, such as collagen. The proposed study will address this unmet challenge by developing a new and sophisticated two component “dual gel†biomaterial using powerful microfluidics research methods. A user-friendly computer program will also be developed and shared with the science community to facilitate applications of such dual-gel materials. The proposed biomaterials can be readily adapted to study various cell types and thus potentially benefit a broad range of fundamental biomedical research questions. Ultimately these new biomaterials could help researchers understand questions like how tissue grows and how cancer cells spread. Moreover, the educational program will provide research opportunities and mentoring to students from high school to graduate levels on both research and career development. The outreach activities include developing science workshops and holiday lecture series for families to bring science and biotechnology to the local community.
This project will develop and use biomaterials to investigate the effects of interstitial flow on cell behavior. Interstitial flow, the slow flux of fluid occurring in the interstitial space of the extracellular matrix (ECM), is linked to ECM permeability and provides direct mechanical cues to the resident cells through shear and normal stress. Moreover, interstitial flow couples with biomolecular diffusion to induce chemotactic signals. This project seeks to investigate the mechanisms regulating cell migration under interstitial flow by designing biomaterials to manipulate interstitial fluid velocity and ECM permeability without affecting other contributing factors, such as stiffness and physical confinement. Achieving this independent control remains a daunting task in traditional hydrogel-based culture models due to the inevitable correlation among various properties of a hydrogel. The proposed research will overcome this challenge by developing tissue-mimetic, dual-gel 3D cell culture matrices that enable independent control of matrix properties, including stiffness, permeability, confining pore size, cell-binding motifs, and interstitial fluid flow. Moreover, the project will demonstrate the capability of the dual-gel matrix to co-culture multiple cells with regulated spatial distribution and cell number ratio. The proposed dual-gel culture models will be fabricated by a combination of two microfluidics approaches. The project will also develop a GUI computer program in MATLAB for numerical visualization of coupling between fluid flow and molecular diffusion in dual-porosity materials. The educational outreach targets on providing research opportunities and mentoring to students from high school to graduate levels in both research and career development. The outreach program will also develop science workshops and holiday lecture series for families to bring science of soft matter, transport phenomena, and biotechnology to the local community.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
