Research Summary

My research interest mainly lies in biomaterials science, cellular mechanics and tissue engineering.

The Global aim of my doctoral research is:
use bioplymers to build up physiologically relevant scaffolds, which closely mimic extracellular matrix (ECM) in real tissue with controlled mechanical and biochemical properties; understand how cells (human dermal fibroblast) interact with these ECM mimics and how these interactions, especially physical interactions (cellular traction forces), regulate cell function and behaviors, which in turn would provide fundamental knowledge for specific tissue engineering design.

I am also working on projects of en masse cell migration, impaired function of aging cells, cell-nanoparticle interactions, and mechanical evaluation of skin substitutes.

Cell-substrate interaction: A tissue-engineered hydrogel composed of cross-linked thiol-modified hyaluronan (HA-DTPH) and cysteine-tagged fibronectin functional domains (FNfds) was developed as a physiologically relevant ECM mimic. The stiffness and adhesiveness of this hydrogel was independently altered by varying crosslinker density or ligand (FNfds) type/density, respectively. The effects of these different substrate properties were studied on cell adhesion, spreading, migration and proliferation. Further more, cellular traction stresses (force per area) were measured by using a novel method, optimized digital image speckle correlation (DISC) technique combined with finite element modeling (FEM).

Cell-cell interaction: En masse cell migration was evaluated by agarose droplet migration assay, to represent cell behavior in certain physiological processes, such as wound repair. Compared with single cell migration under the same conditions, en masse cells perform different responses to the variable of substrate properties, which demonstrates that cell density is another crucial parameter to influence cell migration besides substrate stiffness and cell-substrate adhesiveness.

Focal adhesion & cell stiffness: The stiffness of living cells was measured by using AFM shear modulation force microscopy. It is found to be a good mechanical indicator for cellular traction forces, since both of them were related to the arrangement of cytoskeleton and distribution of focal adhesions.

Cell-nanoparticle interaction: The cytotoxicity of TiO2 nanoparticles in living human dermal fibroblasts was evaluated by studying the proliferation, morphology, and migration of cells exposed to TiO2 nanoparticles at various sizes, concentrations and crystallographic structures. The nanoparticle penetration may induce consequent enormous damages to cells. A dense grafted polymer brush coating on the particles are shown to prevent adherence to the cell membrane and hence penetration of the cell, which effectively decreases reactive oxygen species (ROS) formation and protects cells.

Aging cells: Dermal fibroblasts obtained from different aged subjects demonstrated distinct ability to migrate and contract collagen matrix under the same conditions. With increasing age, cells were also noticed to be inert to the mechanical properties of their environment. To understand these phenomena, both cytoskeleton and integrins of aging cell are being investigated, which are crucial elements during cytoskeleton-dependent mechanotransduction processes. These factors are all relevant to wound healing process and may explain the clinical problems of diminished wound healing for aged people.

Mechanical evaluation of skin substitutes: Use tensiometry to compare the tensile modulus and strength of normal tissue and its artificial replacement. Apply digital image speckle correlation (DISC) technique during tensile test to localize the stain distribution on sample surface which further evaluates the performance of tissue substitutes.

Facial analysis: Digital image speckle correlation (DISC) technique was applied to analyze facial motion, which successfully monitored the recovery of a Bell’s palsy patient.

 

Peer-reviewed publications:
1. Ghosh K, Pan Z, Guan E, Ge SR, Liu YJ, Nakamura T, Ren XD, Rafailovich M, and Clark RAF. “Cell adaptation to a physiologically relevant ECM mimic with different viscoelastic properties”, Biomaterials, 28: 671-679, 2007.

2. Pan Z, Lee W, Slutsky L, Clark RAF, Pernodet N, and Rafailovich M. “Adverse effects of titanium dioxide nanoparticles on human dermal fibroblasts and how to protect cells”, Small, published online ahead of print, 2008.

3. Pan Z, Ghosh K, Liu YJ, Clark RAF, and Rafailovich M. “Traction stresses and translational distortion of the nucleus during fibroblast migration on a physiologically relevant ECM mimic”, Biophysical Journal, in press, 2009

4. Lin F, Ren XD, Pan Z, Macri L, Zhong WX, Mosher DF, Tonnesen MG, Rafailovich M, Bar-Sagi D, and Clark RAF, “Fibronectin growth factor-binding domains are required for fibroblast survival”, submitted, 2008.

5. Pan Z, Ghosh K, Liu YJ, Clark RAF, and Rafailovich M. “Investigate cellular mechanical responses to fibronectin functional domains on a physiologically relevant ECM mimic”, ready to be submitted, 2009.

6. Pan Z, Ghosh K, Hung V, Macri L, Clark RAF, and Rafailovich M. “Cell density modulates cell migration: single-cell versus en masse migration”, in preparation.

7. Pan Z, Ghosh K, Liu YJ, Ge SR, Lin F, Clark RAF, and Rafailovich M., “The effects of chronological age on the cellular mechanics of human dermal fibroblasts: a potential mechanism of poor wound healing in the elderly”, in preparation.

Conference talk and posters:
Pan Z, Ghosh K, Guan E, Liu YJ, Ren XD, Shu XZ, Ge SR, Nakamura T, Prestwich GD, Clark RAF, Rafailovich M. “Cellular traction forces on hyaluronic acid substrates with different fibronectin functional domains”, MRS Annual Fall Meeting, Boston, MA, Nov 2005 (Oral).

Pan Z, Ghosh K, Liu YJ, Ge SR, Shu XZ, Nakamura T, Prestwich GD, Clark RAF, Rafailovich M. “The effects of chronological age on the cellular mechanics of human dermal fibroblasts”, APS March Meeting, Baltimore, MD, March 2006 (Oral).

Pan Z, Fang XH, Lee W, Pernodet N, Rafailovich M. “The penetration of titanium dioxide nanoparticles: from dermal fibroblasts to skin tissue”, APS March Meeting, Baltimore, MD, March 2006 (Oral).

Pan Z, Ghosh K, Liu YJ, Hung V, Kambhampati S, Ge SR, Nakamura T, Clark RAF, Rafailovich M. “Human dermal fibroblasts demonstrate diminished ability to generate traction forces with chronological age: A potential mechanism of poor wound healing in the elderly”, Society for Investigative Dermatology (SID) Annual Meeting, Philadelphia, PA, May 2006 (Poster).

Pan Z, Ghosh K, Liu YJ, Shu XZ, Ge SR, Nakamura T, Prestwich GD, Ren XD, Clark RAF, Rafailovich M. “Cellular traction forces of adult human dermal fibroblasts in response to fibronectin functional domains: from biochemical signals to mechanical responses”, MRS Annual Fall Meeting, Boston, MA, Nov 2006 (Oral).

Pan Z, Ghosh K, Hung V, Shu XZ, Prestwich GD, Clark RAF, Rafailovich M. “The dynamics of cell migration on hyaluronic acid hydrogel surface”, MRS Annual Fall Meeting, Boston, MA, Nov 2006 (Poster).

Pan Z, Ge SR, Ghosh K, Shu XZ, Prestwich GD, Clark RAF, Rafailovich M. “Age-related cellular mechanical study using AFM shear modulation force microscopy”, MRS Annual Fall Meeting, Boston, MA, Nov 2006 (Poster).

Pan Z, Clark RAF, Ghosh K, Liu YJ, Shu XZ, Nakamura T, Prestwich GD, Rafailovich M. “Fibroblast migration requires co-operative rearward and forward traction gradients across the whole cell and the nucleus, respectively”, SID Annual Meeting, Los Angeles, CA, May 2007 (Oral).

Pan Z, Liu YJ, Ghosh K, Nakamura T, Clark RAF, and Rafailovich M. “Instantaneous distribution of cellular tractions during fibroblast migration”, ACS Fall National Meeting, Boston, MA, Aug. 2007 (Poster).

Pan Z, Lin F, Clark RAF, Rafailovich M. “Focal adhesion influence on cell stiffness and cell survival”, MRS Annual Fall Meeting, Boston, MA, Nov 2007 (Poster).

Pan Z, Lee W, Slutsky L, Clark RAF, Pernodet N, and Rafailovich M. “Adverse effects of titanium dioxide nanoparticles on human dermal fibroblasts and how to protect cells”, MRS Annual Fall Meeting, Boston, MA, Nov 2008 (Poster).

Pan Z, Liu YJ, Ghosh K, Nandamudi D, Stemp D, Nakamura T, Clark RAF, and Rafailovich M. “Imaging spatiotemporal redistribution of cellular traction stresses during fibroblast migration on a physiologically relevant ECM mimic”, APS March Meeting, Pittsburgh, PA, March 2009 (Oral).

Research mentoring for summer program:
I love to share my interest and enthusiasm for my research with students who really love science Teaching with interaction is enjoyable experience.

Swetha Kambhampati (University High School, Irvine, CA) and
Victoria Hung (Smithtown High School, Smithtown, NY) Summer-Fall 2005
Project title: Enhancing mechanotransduction of aging human dermal fibroblasts for improved wound healing 
Honor won: Semifinalists at Siemens-Westinghouse Competition (10/2005)

Victoria Hung (Smithtown High School, Smithtown, NY ) Summer-Fall 2006
Project title: Mathematical modeling of fibroblast migration 
Honor won: Semifinalist at Intel Science Talent Search (STS) (1/2007)

Dhruv Nandamudi (Monta Vista High School, Cupertino, CA) and
Daniel Stemp (North Shore Hebrew Academy High School, Great Neck, NY) Summer-Fall 2007
Project titled: Optimized cell migration on functionalized surfaces  
Honor won: Regional finalists at Siemens-Westinghouse Competition (11/2007)

With my students:

My son Leo, born on 7/28/2008 made me miss the summer program in 2008. He was the biggest honor I won in last year

My interest besides research and teaching:
Travel, photography, and food.