Precise control of directional migration and spatial organization of multiple cell types is critical to maintaining and engineering tissue function. A major challenge in biomaterials research is the design and fabrication of biomaterials that can guide the simultaneous self-assembly of large number of cells with the precision and efficiency of biological systems. The proposed research builds on the PI and co-PI's recent discovery of MANDIP - Microarray Amplification of Natural Directional Persistence - to guide the long-range directional migration of attached mammalian cells. Key to MANDIP and the natural directional persistence of freely migrating cells is that the envelope of extended lamellipodia is preferentially aligned to the extended cell body. Through an asymmetric arrangement of cell adhesive microarray islands that acts as a ratchet by restricting lamellipodia attachment, MANDIP imposes directionality with overwhelming compliance, guiding simultaneously the migration of unlimited number of cells independently over arbitrary preset paths of unlimited distance without chemoattractants external fields, or mechanical manipulation. The objective of this proposal is to establish a foundation of MANDIP design strategies whose transformative impact will be demonstrated through the following specific aims:
Aim 1 : Design one-way micropatterns to guide the directional migration of cells on biomaterials, Aim 2: Direct self-assembly of multiple cell types to mimic liver tissue and promote vascularization, Aim 3: Devise a biological analogue of thin-layer chromatography for sorting cells by their intrinsic motility. Accomplishing these aims will bring to fruition MANDIP's potential in promoting tissue pattern formation and as a ubiquitous low-cost cell-sorting platform analogous to thin layer chromatography.

Public Health Relevance

The application is relevant to public health as a low-cost cell sorting technology for rapid screening/purification of cells or diagnosis of diseases related to cell motility and can be applied to engineer tissues by 3D scaffolds that direct migration of multiple cell types.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB010043-03
Application #
8214559
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Hunziker, Rosemarie
Project Start
2010-02-01
Project End
2014-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
3
Fiscal Year
2012
Total Cost
$336,405
Indirect Cost
$120,135
Name
University of Cincinnati
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
041064767
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Michel, Daniel R; Mun, Kyu-Shik; Ho, Chia-Chi et al. (2016) Cytoskeletal architecture and cell motility remain unperturbed in mouse embryonic fibroblasts from Plk3 knockout mice. Exp Biol Med (Maywood) 241:603-10
Andrews, Ross N; Co, Carlos C; Ho, Chia-Chi (2016) Engineering Dynamic Biointerfaces. Curr Opin Chem Eng 11:28-33
Kumar, Girish; Ho, Chia-Chi; Co, Carlos C (2015) Cell-Substrate Interactions Feedback to Direct Cell Migration along or against Morphological Polarization. PLoS One 10:e0133117
Wang, Xiao; Zandi, Matthew; Ho, Chia-Chi et al. (2015) Single stream inertial focusing in a straight microchannel. Lab Chip 15:1812-21
Chen, Bo; Co, Carlos; Ho, Chia-Chi (2015) Cell shape dependent regulation of nuclear morphology. Biomaterials 67:129-36
Ko, Young-Gwang; Co, Carlos C; Ho, Chia-Chi (2013) Gradient-free directional cell migration in continuous microchannels. Soft Matter 9:2467-2474
Andrews, Ross N; Mun, Kyu-Shik; Scott, Carl et al. (2013) Rapid Prototyping of Heterotypic Cell-Cell Contacts. J Mater Chem B Mater Biol Med 1:5773-5777
Mun, Kyu-Shik; Kumar, Girish; Co, Carlos C et al. (2013) Micropatterning different cell types with microarray amplification of natural directional persistence. Adv Healthc Mater 2:334-42
Chen, Bo; Kumar, Girish; Co, Carlos C et al. (2013) Geometric control of cell migration. Sci Rep 3:2827
Ko, Young-Gwang; Co, Carlos C; Ho, Chia-Chi (2013) Directing cell migration in continuous microchannels by topographical amplification of natural directional persistence. Biomaterials 34:353-60

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