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Investigate Cellular Responses for Environmental Cues

Investigate Cellular Responses for Environmental Cues. Qian Wang Department of Chemistry and Biochemistry, and Nanocenter University of South Carolina, SC, USA. Cell shape determines fate of stem cells. Flower Star. Star shape and flower shape expressed different differentiation profile

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Investigate Cellular Responses for Environmental Cues

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  1. Investigate Cellular Responses for Environmental Cues Qian Wang Department of Chemistry and Biochemistry, and Nanocenter University of South Carolina, SC, USA

  2. Cell shape determines fate of stem cells Flower Star Star shape and flower shape expressed different differentiation profile Flower shape promoted adipogenesis Star shape promoted osteogenesis Mrksich M., et al. PNAS, 2010, 16, 4872-4877

  3. ECM Mimetic Substrates Natural ECM architecture ECM mimetic substrates 50um Abrams, G. A., et al., Cell Tissue Res , 2000, 299, 39-46 Kim, D. H. et al., PNAS , 2010, 107,565-570 Roohani-Esfahani, S.I., et al., Biomaterials , 2010, 31, 5498-5509 Pham, Q. P. et al., Tissue Eng , 2006, 12, 1197-211

  4. Models of Tumor Heterogeneity Nature 414:105, 2001

  5. Are We Targeting the Right Cancer Cells? Dr. Xinfeng Liu Mathematician • Major Challenges: • Lack of universal biomarker • Lack of In vitro cell culture model Dr. Hexin Chen Biologist Nature 414:105, 2001 Sarkar, B. ; Dosch, J., et al. Chem. Rev. 2009, 109, 3200–3208

  6. A Novel Breast Cancer Stem Cell Model - H6O5 Cells • Her2/neu induced mouse mammary tumor • Consists of a highly tumorigenic population (CSCs) • Isolated based on two integrin markers CD49f and CD61 • Confirmed by its in vivo tumorigenicity CD49f CD61 Fluorescence assisted cell sorting Lo, P. K., et al., Oncogene2012, (doi: 10.1038/onc.2011.439)

  7. H6O5 Cells on Fiber Substrate Aligned fiber substrate Culture for 3- 5 days Tissue culture well H6O5 • Morphology • EMT- associated gene expression

  8. Morphology of Electrospun Fiber Substrate Poly-Caprolactone Biodegradable Cytocompatible Aligned Fiber Random Fiber A SEM images of aligned (d = 1.8 ± 0.46 μm) and random (d = 2.0 ± 0.65 μm) Scale bar = 20 μm Saha. S et al.,Langmuir, 2012, 28, 2028-2034

  9. Morphology of H6O5 Cells on Aligned Fiber Substrate a b 10x 10x • Cell attach to fiber • Elongated morphology • Growth, • Proliferation • Maintain elongated morphology Green: actin cytoskeleton Blue: nuclei White arrows: underlying fiber direction, Scale bar = 40 µm 10x S. Saha et al. Langmuir, 2012, 28, 2028-2034

  10. Enrichment of Cancer Stem Cells Using Nano-fibrous Scaffolds S. Saha et al. Langmuir, 2012, 28, 2028-2034

  11. Enhanced Expression of EMT Markers of MCF-7 Cells Gene expression by qRT-PCR S. Saha et al. Langmuir, 2012, 28, 2028-2034

  12. ALDH (Aldehyde Dehydrogenase) Activity of MCF-7 Cells Aligned Fiber Random Fiber A Sheng Feng

  13. Increased Mammosphere-Forming Capability Aligned Fiber Random Fiber A Sheng Feng

  14. Increased Invasion Property of Epithelial Breast Cancers Cells Cultured On PCL Fiber Aligned Fiber Random Fiber A Sheng Feng

  15. Results of MDA-MB-231 Cells Cultured from PCL Fiber Aligned Fiber Random Fiber A Sheng Feng

  16. A Hypothesis of the Double-Feedback to Control the CSCs Fate A Dr. Xinfeng Liu, Hexin Chen

  17. Alignment of Rod Like Nanoparticles O. D. Velev et al, Small 2006, 2, 1462 Zhongwei, Jianhua, Mike Bruckman

  18. 2D Alignment of Colloidal Particles Dimitrov and Nagayama, Langmuir 1996, 12, 1303

  19. 2D Alignment of Protein Nanoparticles O. D. Velev et al, Small 2006, 2, 1462 Mike Bruckman, Zhongwei Niu

  20. Controlled Alignment of Cell Growth Jianhua Rong, Zhongwei Niu, in collaboration with Dr. Charlene Mello

  21. Cardiovascular Disease in USA United States, 2004. Source: NCHS and NHLBI Rosamond W et al., Circulation 2008, 117 (4): e25-146

  22. Vascular Disorders and Pathogenesis of Atherosclerosis VSMC Normal form VSMC Proliferative form Osterud & Bjorklid; Physiol Rev. 2003, 83, 1069-112

  23. Smooth Muscle Cells: Different Morphologies Lilly

  24. Contractile and Synthetic Morphology Aligned Scaffold Control

  25. Significance of the Alignment of Smooth Muscle Cells

  26. Are There a Good Model to Predict/Explain The Cellular Responses to Contact Cues??

  27. Are There a Good Model to Predict/Explain The Cellular Responses to Contact Cues??

  28. Acknowledgments Sheng Feng Hong Guan Clorissa Washington Yixing Cheng Enoch Adogla Iin Lv Gift Metavarayuth Peiyi Wang Fang Zhou (CIAC) Xia Zhao (CIAC) Limin Chen (CIAC) Many talent undergrad. Wang Group: L. Andrew Lee (Postdoc) Xinrui Duan (Postdoc) Honglin Liu (Postdoc) Jun Hu (Postdoc) Pan He (Research Ass.) Dan Menasco Nikki Sitasuwan Matsepo Ramaboli Amie J. Luckanagul BNP Assembly: Tom Russell (UMass) Yao Lin (UConn) Alex Böker (MPI) P. Thiyagarajan (DOE) Byeongdu Lee (ANL) Lin Yang (BNL) Z. Su (CIAC, CAS) C. Xiaodong Li (USC) Wenke Zhang (Jilin U) Cell Study Hexin Chen (USC) Tara Soto-Atwood (UF) J. Potts (USC) Protein Binding Study Lukasz Lebioda (USC) Frank Berger (USC) Virus: Theo Dreher (OSU) Rick Nelson (Noble) Charlene Mello (ARL) Peter E. Prevelige (UAB) Polymeric Assembly: Mihaela Stephan (UTD) Yuan Lin (CIAC, CAS) Simulation Qi Wang (USC) Xinfeng Liu (USC) $$$ NSF-CAREER/NSF-DMR NIH-COBRE Sloan/Camille Dreyfus DOD-ARO DOE-BES W. M. Keck Foundation SC EPSCoR Office & SCCC Wang Group Alumni: Yi Chen (Res. Professor) Gary Horvath (S. Scientist) Postdoc: K. Sivakumar S. Chittaboina V.S. Kotakadi Zhongwei Niu Qingbing Zeng Céline le Droumaguet Jianhua Rong Yuan Lin Jiangli Fan Xingjie Zan Undergraduate Student: Lisa Alexander Giang Nguyen …… Graduate Student: Hannah Barnhill Fang Xie Su Long Brandon Cash Saswat Kabisatpathy Siqi Li Mike Bruckman Gagandeep Kaur Tao Li Kai Li Chao Wang Jerry Oxsher Laying Wu Eve Suthiwangcharoen Sharmi Saha Lilly Balizan

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