Development of Cell Manipulation Tools for Probing Functional Mechanism of Hematopoietic Cells: Robotics, Optical tweezers, and Hematopoiesis

Description

Cell functions are controlled by individual biomolecules and their interactions. However,the understanding of individual cell mechanisms at a fundamental and integrated levelremains elusive thus far. A significant challenge lies in the lack of efficient tools that can beused for probing and controlling cellular behaviors with micro/nano-scale level precision. Inthis proposal, we propose to develop generic automated cell manipulation tools utilizingrobotically controlled optical tweezers. To demonstrate the efficacy of these sophisticatedexperimental tools, hematopoietic cells are manipulated to probe the functional mechanism ofhematopoiesis, a highly conserved and critical process that arises from and is sustained by arare population of hematopoietic stem cells (HSC). Abnormal regulation of HSC and theirprogenitors (HSPC) leads to serious diseases such as acute myeloid leukemia (AML), a lethalform of cancer affecting appropriately every one in 250 people.In this proposed research, manipulation and probing the functional mechanism of cells willbe realized by developing a Cell Bio-Probe that integrates robotics, optical tweezers, andmicrofluidics based on micro-electro-mechanical system (MEMS) and nanotechnology. TheCell Bio-Probe will include optical manipulation tools that can enable several keymanipulation tasks, such as: cell stretching, cell adhesion, and cell transportation. Therobotically controlled system will allow either a single cell, or simultaneously many cells tobe tested and probed. This will enable the key cell properties to be characterized over apopulation of cells, further refining our understanding of cell properties. The Cell Bio-Probewill be used to probe the mechanism of hematopoiesis from the following three perspectivesto: i) characterize the mechanobiological properties of hematopoietic cell with reference to itslink to abnormal differentiation; ii) investigate the molecular mechanism that regulatesinteractions between HSPC and AML cells with stromal cells; iii) study the migrationmechanism of hematopoietic cell trafficking to the bone marrow.The success of this research will advance biomedical engineering science towardsunderstanding the functional mechanism of cells. Investigation with the proposed CellBio-Probe to hematopoietic cells will provide hitherto novel and dynamic informationrevealing the aberrant regulation of HSPC that leads to AML, with the potential to identifynovel targets which may lead towards the eradication of this disease. Although the CellBio-Probe is mainly focused on the hematopoietic cells in this research, the generatedresearch outcomes will also serve as important references for other cell types for thedevelopment of therapies to combat other serious human diseases.