Highly Sensitive Electrostatic Sensors and Programmable Stiffness Actuators for Cell Migration Manipulation

Description

Cell migration is vital to numerous biological processes, and defining the mechanical properties can enhance physiological research and lead to methods to intervene pathological conditions. For instance, cell migration plays a critical role in tissue formation during the embryonic development of multicellular organisms. The directed migration of fibroblasts, vascular endothelial cells, and leukocytes is also essential for successful would-healing and inflammatory responses. On the other hand, cancer cell migration from the initial tumor mass into the circulatory system leads to invasion and metastasis. Therefore, research on cell migration has primarily focused on identifying the specific molecular components that work together dynamically for the purpose of understanding the chemical and physical properties of each component in the systemic assembly. This type of integrated cell migration research will prove integral for both diagnoses and therapies for pathological conditions, as well as providing the basis for pharmacological or material-based intervention.The functions that regulate cell migration are directly affected by the physical interactions with the surrounding environment. For instance, cells have demonstrated the ability to sense and transport mechanical signals into the internal cytoskeleton. Moreover, multiple proteins have been shown to work in coordination during the signal pathways for cell migration. The forces of cell traction are integral for cell migration and determine both motility and directionality. We propose to investigate methods tomeasure and control cell migration using a highly sensitive traction force sensor array and a programmable actuator that can sequentially tune the stiffness gradient for manipulating single cells and directing multiple cell interactions. Our objectives include the following: (1) design, fabricate, and testhighly sensitive cell traction force sensor arrays(nano-Newton range) with electrostatic comb drives and patterned trails to provide directional cell guidance; (2) design, fabricate, and test programmable actuator arrays to tune stiffness of stretchable membrane to dynamically alter stiffness gradients and to control pathways for cell migration and interactions; (3) develop coating technologies for formingconformal insulating layersaround the comb electrodes to prevent shorting and corrosion, to investigatestretchable elastomers and gelswith designed properties, and to develop reversal imprint technologies to transfer patterned membranes onto comb-drive actuators; (4) measure andanalyze cell traction forcesgenerated at different locations within a cell during cell migration and directional changes, and to relate force changes to changes in cell motility and migration directionality; and (5)manipulate cell migration by sequential programming of electrostatic comb-drive actuators, to demonstratecontrol of single cell migration pathways, and to steer multiple cells to specified locations to promotecell interactions or cell selections.The proposed platform offers ahighly sensitive electrostatic traction force sensor arraythat can provide new insight into theinvestigation of the complex system of cell migration. Furthermore, the proposed platform can also function as aprogrammable actuator to dynamically tune stiffness gradients to manipulate the temporal properties of cell migration interactions.Together, these two functions can be combined to provide the ability to monitor and control cell migration to benefit numerous biological processes such as embryo development, wound healing, immune responses, and intervening cancer metastasis. The long-term impact of this combined sensor and actuator microsystem will be profound due to the numerous biomedical applications that require the control of cell migration for rapid disease diagnosis in order to provide early preventative measures and treatment efficacy.