2014 Fiscal Year Research-status Report
Establishing the Design Principles to Control the Directional Cell Motility on Material Surface Topographies
|Research Institution||The University of Tokyo |
久代 京一郎 東京大学, 工学(系)研究科(研究院), 助教 (90632539)
|Project Period (FY)
2014-04-01 – 2016-03-31
|Keywords||microtopography / directed cell migration|
|Outline of Annual Research Achievements
In recent years, the effects of material topography and shapes on cellular behaviors have gained much attention and interest for the purpose of designining novel biomaterials for tissue engineering and clinical applications. The initial interest of this project was to investigate the 3D surface-topographical cues to direct the migration of cells within micropatterned 3D microchannels, and to investigate different topographical cues to distinguish cancerous and non-cancerous cells.
Using an open PDMS microchannel system (microgrooves), we found different migratory behaviors on these structures among different cell types. Non-cancerous cells tended to align along the walls of the microgroove structures, as well as take on a unilamellar morphology that enhanced their migration speed and persistence. On the other hand, the cancerous cells were more non-polarized overall and whenever they contact the walls, they would usually detach within a short time span (they have low persistence length). An interesting observation, however, was that the cancerous cells could climb over certain types of walls, and th effects of different wall angles and material elasticity were investigated as well. From these results, it can be said that it was possible to distinguish cancerous and non-cancerous cells using microtopographical cues.
Although slightly different from the initial plan, further progress in this research may more chaeply and simply enable the identification and separation of cancerous cells from non-cancancerous cells without the use of traditional antibody-based methods.
|Current Status of Research Progress
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Although the initial plan of using the micropatterned microchannels to control the directional migration of non-cancerous and cancerous cells did not yield much concrete results, we were able to achieve the bigger objective of dinstinguishing and potentially isolating cancerous cells from non-cancerous (normal) cells using the differences in response to topographical cues. More specifically, we found a very interesting phenomenon that cancerous cells, which are known to often lack the polarization capabilities, can climb the walls of microgrooves with specific height and angle. This was dinstinctively different from the normal cells tested (both epithelial and prostate cell types) that would adhere and change their morphology to align against the walls of the microgrooves. Using these differences, it is likely possible to separate out cancerous cells from non-cancerous cells by creating devices embedded with these microgroove topographies.
Regarding the other objective of effectively controlling the directional movement of cells using the 3D microtopography structures, we will continue to test out other asymmetrical wall structures that may be able to guide the direction of cell migration, and in a different fashion for normal and cancerous cells.
|Strategy for Future Research Activity
Plans for the future works involve the creation of a specially designed microdevices that would be able to separate out the cancerous cells and non-cancerous cells using the understandings obtained from the research thus far. In order to do so effectively, we would also investigate the underlying mechanotransduction mechanism that is causing such drastic differences. In addition to immunostaining methods, in collaboration with other professors, we are looking at genetically manipulated variations of the epithelial cells to pin-point the exact genes and proteins responsible for these behaviors. We are also interested in collective cell migration (as opposed to the single cell migrations observed thus far), and aim to look at similar phenomenon using cell clusters. Finally, we are also interested in sorting stem cells from differentiated cells by using similar methodologies.
Regarding the other objective of effectively controlling the directional movement of cells using the 3D microtopography structures, we will continue to test out other asymmetrical wall structures that may be able to guide the direction of cell migration, and in a different fashion for normal and cancerous cells or for stem cells and differentiated cells.
Research Products (3 results)