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
Flower shape promoted adipogenesis
Star shape promoted osteogenesis
Mrksich M., et al. PNAS, 2010, 16, 4872-4877
ECM Mimetic Substrates
Natural ECM architecture
50um
ECM mimetic substrates
Abrams, G. A., et al., Cell Tissue Res , 2000, 299, 39-46
Roohani-Esfahani, S.I., et al., Biomaterials , 2010, 31, 5498-5509
Kim, D. H. et al., PNAS , 2010, 107,565-570
Pham, Q. P. et al., Tissue Eng , 2006, 12, 1197-211
Models of Tumor Heterogeneity
Nature 414:105, 2001
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
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
NMuMG
H6O5
CD49f
G1: CD49fhighCD61high
G2
G1
G3
G2: CD49fhighCD61low
CD49f
G3: CD49flowCD61low
Fluorescence assisted
cell sorting
CD61
CD61
CD49f highCD61low
CD49f highCD61high
Lo, P. K., et al., Oncogene 1.2
2012, (doi: 10.1038/onc.2011.439)
89.9
74.0
2.7
CD49f lowCD61low
2.0
25.4
H6O5 Cells on Fiber Substrate
Aligned fiber substrate
H6O5
Tissue culture well
Culture for 3- 5 days
•
Morphology
•
EMT- associated gene
expression
Morphology of Electrospun Fiber
Substrate
Poly-Caprolactone
Biodegradable
Cytocompatible
A
Aligned Fiber
Random Fiber
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
Morphology of H6O5 Cells on Aligned
Fiber Substrate
a
b
10x
• Cell attach to fiber
• Elongated morphology
Green: actin cytoskeleton
Blue: nuclei
White arrows: underlying fiber direction,
Scale bar = 40 µm
10x
• Growth,
• Proliferation
• Maintain elongated morphology
10x
S. Saha et al. Langmuir, 2012, 28, 2028-2034
Enrichment of Cancer Stem Cells Using
Nano-fibrous Scaffolds
S. Saha et al. Langmuir, 2012, 28, 2028-2034
Fold difference
Enhanced Expression of EMT Markers of
MCF-7 Cells
13
12
11
10
9
8
7
6
5
4
3
2
1
0
TCP
Random PCL fiber
Aligned PCL fiber
Ck18
Ck14
Sma TGFβ1 snail
Stat3
Fsp1 Smad3
Gene expression by qRT-PCR
S. Saha et al. Langmuir, 2012, 28, 2028-2034
ALDH (Aldehyde Dehydrogenase) Activity
of MCF-7 Cells
A
Aligned Fiber
Random Fiber
Sheng Feng
Increased Mammosphere-Forming
Capability
A
Aligned Fiber
Random Fiber
Sheng Feng
Increased Invasion Property of Epithelial
Breast Cancers Cells Cultured On PCL Fiber
A
Aligned Fiber
Random Fiber
Sheng Feng
Results of MDA-MB-231 Cells Cultured
from PCL Fiber
A
Aligned Fiber
Random Fiber
Sheng Feng
A Hypothesis of the Double-Feedback to
Control the CSCs Fate
A
Dr. Xinfeng Liu, Hexin Chen
Alignment of Rod Like Nanoparticles
Zhongwei, Jianhua, Mike Bruckman
O. D. Velev et al, Small 2006, 2, 1462
2D Alignment of Colloidal Particles
Dimitrov and Nagayama, Langmuir 1996, 12, 1303
2D Alignment of Protein Nanoparticles
Mike Bruckman, Zhongwei Niu
O. D. Velev et al, Small 2006, 2, 1462
Controlled Alignment of Cell Growth
Jianhua Rong, Zhongwei Niu, in collaboration with Dr. Charlene Mello
Cardiovascular Disease in USA
United States, 2004. Source: NCHS and NHLBI
Rosamond W et al., Circulation 2008, 117 (4): e25-146
Vascular Disorders and
Pathogenesis of Atherosclerosis
VSMC Normal form
Osterud & Bjorklid; Physiol Rev. 2003, 83, 1069-112
VSMC Proliferative form
Smooth Muscle Cells: Different Morphologies
Lilly
Aligned
Scaffold
Control
Significance of the Alignment of
Smooth Muscle Cells
Are There a Good Model to Predict/Explain
The Cellular Responses to Contact Cues??
Are There a Good Model to Predict/Explain
The Cellular Responses to Contact Cues??
Acknowledgments
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
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 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
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