Molecular Biophysics and Bioengineering Physics


Our research at Texas Tech focuses on various areas of biological systems spanning the molecular, cellular, tissue (device) and human levels. At the molecular and cellular level, we are interested in the molecular organization and dynamics of the self-assembling lipid bilayer, an important component of the cell membranes, and the molecular mechanisms of its regulation of protein activities, e.g., calcium flux regulation by ion channels, antigen-antibody binding, protein binding and enzyme-mediated cholesterol oxidation. At the tissue or device level, we are interested in the chemistry of the radiation-induced polymerization of gel materials, the development of computational algorithm for quantitative magnetic resonance imaging (QMRI) and development of cell-based biochips. Our work in lipid bilayer has applications in the development of biosensors and drug-delivery liposomes. The work on QMRI has application in the dose verification and design of multi-dimensional conformal radiation therapy for cancer treatments. The work on biochips has practical applications in in-vitro cancer cell detection and drug delivery efficacy in tumor microvasculature. Finally, at the human level, we are interested in the area of physics education, particularly on the effect of internet technology on the students' understanding of physics concepts at the undergraduate level.


Research at the Molecular Level
Physics of self-assembling lipid bilayer in liposomes and solid-supported single bilayer on microchips (Lipid-Chips)

Our research interests at the molecular level are focused on studying the rotational dynamics, intra- and inter-molecular dynamics and lateral organization of self-assembling lipid molecules in bilayer membranes in the form of suspensions (liposomes) or in solid supported microchannels in biochips. These nanomaterials have interesting and novel applications in designing and creating liposomal drugs, vectors for non-viral based gene transfection and therapy, and functional templates for biosensors. Our techniques include time-resolved fluorescence, infrared and surface fluorescence microscopy. Our recent interests are in cholesterol domains of self-assembling lipid bilayers in both liposomes and in Lipid-Chips. Results

Representative Publications
  • Cheng, K. H. 1989. Fluorescence depolarization study of lamellar liquid crystalline to inverted cylindrical micellar phase transition of phosphatidylethanolamine. Biophysical Journal 55:1025-1031.

  • van der Meer, B. W., K. H. Cheng, and S.-Y. Chen. 1990. Effects of lateral diffusion on the fluorescence anisotropy in hexagonal lipid phase I. Theory. Biophysical Journal 58:1527-1537.

  • Chen, S.-Y., K. H. Cheng, B. W. Van Der Meer, and J. M. Beechem. 1990. Effects of lateral diffusion on the fluorescence anisotropy in hexagonal lipid phase II. An experimental study. Biophysical Journal 58:1527-1537.

  • Cheng, K. H., S.-Y. Chen, P. Butko, B. W. Van Der Meer, and P. Somerharju. 1991. Intramolecular excimer formation of pyrene-labeled lipids in lamellar and inverted hexagonal phases of lipid mixtures containing unsaturated phosphatidylethanolamine. Biophysical Chemistry 39:137-144.

  • Chen, S.-Y., K. H. Cheng, and B. W. Van Der Meer. 1992. Quantitation of lateral stress in lipid layer containing nonbilayer phase preferring lipids by frequency-domain fluorescence spectroscopy. Biochemistry 31:3759-3768.

  • Chen, S.-Y. and K.H. Cheng. 1996. Detection of membrane packing defects by time-resolved fluroescence depolarization. Biophysical Journal 71: 878-884.

  • Cheng, K.H., M. Ruonala, J. Virtanen, and P. Somerharju. 1997. Evidence for superlattice arrangements in fluid phosphatidylcholine/phosphatidylethanolamine Bilayers. Biophysical Journal 73: 1967-1976.

  • Virtanen, J.A., K.H. Cheng and P. Somerharju. 1998. Phospholipid composition of the mammalian red cell membrane can be rationalized by a superlattice model. Proc. Natl. Acad. Sci. USA. 95: 4964-4969.

  • Somerharju, P., J. A. Virtanen and K.H. Cheng. 1999. Lateral Organization of membrane Lipids. The Superlattice View. (Review) Biochimica et Biophysica Acta 1440: 32-48.

  • Cheng, K.H., J. Virtanen and P. Somerharju. 1999. Fluorescence Studies of Dehydroergosterol in Phosphatidylethanolamine/ Phosphatidylcholine Bilayers. Biophysical Journal 77: 3108-3119.

  • Tanhuanpaa K., K. Cheng, J. Virtanen, K. Anttonen and P. Somerharju. 2001. Characteristics of Pyrene Phospholipid/gama-Cyclodextrin Complex. Biophysical Journal 81: 1051-1510.

  • Brian Cannon, Garrette Heath, Juyang Huang, Pentti Somerharju, Jorma Virtanen, and Kwan Hon Cheng. 2003. Time-Resolved Fluorescence and Fourier Transform Infrared Spectroscopic Investigations of Lateral Packing Defects and Superlattice Domains and in Compositionally Uniform Cholesterol/Phosphatidylcholine Bilayers. Biophysical. Journal. 84: 3777-3791

  • Cannon, B., N. Weaver, Q. Pu, V. Thiagarajan, S Liu, J. Huang, M. W. Vaughn, and K. H Cheng.2005. Cholesterol modulated antibody binding in supported lipid membranes as determined by total internal reflectance microscopy on a microfabricated high-throughput glass chip. Langmuir. 21:9666-9674.

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Research at the Cellular Level
Regulations of Lipid Compositions on Ca-Transport Functions of Proteins and Cell-based biochip

Our research interests at the cellular level are focused on studying the physics of the structure, dynamics, function relationship of lipid and membrane protein molecules in the synthetic, reconstituted and isolated cellular membranes. Obviously those membrane systems are more complicated than the self-assembling lipid membranes above. They provide a unique and well-defined biological system to allow us to study several well-defined cellular components, lipids of defined compositions (e.g., cholesterol and phospholipids of different acyl chain and headgroup compositions) and isolated cellular proteins (e.g., Human Complement Proteins and their membrane attack complex, Calcium pumping enzyme and Calcium channels), in a controlled environment. The results of these cellular level studies will provide new insights about the functions and regulation mechanisms of cells. The research on cell-based biochip focuses on the development of cancer cell capture and tissue mimic that have application in cancer diagnosis and therapy. Results

Representative Publications
  • Lepock, J. R., K. H. Cheng, H. Al-Qysi, and J. Kruuv. 1983. Thermotropic lipid and protein transition in Chinese hamster lung cell membranes. Canadian Journal of Biochemistry 61:421-427.

  • Lepock, J. R., K. H. Cheng, S. D. Campbell, and J. Kruuv. 1983. Rotational diffusion of TEMPONE in cytoplasm of Chinese hamster cell. Biophysical Journal 44:405-412.

  • Kruuv, J., D. Golfcheski, K. H. Cheng, H. Al-Qysi, W. T. Nolan, and J. R. Lepock.1983.Factor influencing survival and growth of mammalian cell exposed to hypothermia. Journal of Cell Physiology 115:175-185.

  • Gruber, M., K. H. Cheng, J. R. Lepock, and J. E. Thompson. 1984. Improved yield of plasma membranes from mammalian cells through modification of two-phase polymer isolation procedure. Analytical Biochemistry 138:112-118.

  • Cheng, K. H., T. Weidmer, and P. J. Sims. 1985. Fluorescence resonance energy transfer study of the membrane bound complexes of complement protein C5b-8. Journal of Immunology 135:459-464.

  • Cheng, K. H., and S. W. Hui. 1986. Correlation between the bilayer destabilization and activity enhancement by diacylglycerols in reconstituted Ca-ATPase vesicles. Archieves of Biochemistry and Biophysics 24:382-386.

  • Cheng, K. H., J. R. Lepock, S. W. Hui, and P. L. Yeagle. 1986. The role of cholesterol in the activity of reconstituted Ca-ATPase vesicles containing unsaturated phosphatidylethanolamine. Journal of Biological Chemistry 261:5081-5087.

  • Legge, R. L., K. H. Cheng, J. R. Lepock, and J. E. Thompson. 1986. Differential effect of senescence on the molecular organization of membranes. Plant Physiology 81:954-959.

  • Lepock, J. R., K. H. Cheng, H. Al-Qysi., I. Sim., C. J. Koch., and J. Kruuv. 1987. Hyperthermia induced inhibition of respiration and mitochondria protein denaturation in CHL cells. International Journal of Hyperthermia 3:123-133.

  • Cheng, K. H., S. W. Hui, and J. R. Lepock. 1987. Protection of the membrane calcium ATPase by cholesterol from thermal inactivation. Cancer Research 47:1255-1262

  • Cheng, K. H. 1989.The role of calcium in the thermal inactivation of calcium transport protein. Cancer Research 49:7026-7030.

  • Lepock, J. R., A.M. Rodahl, Zhang, C., M. L. Heynen, and K. H. Cheng. 1990. Thermal denaturation of the Ca-ATPase of sarcoplasmic reticulum reveals two thermodynamically independent domains. Biochemistry 29:681-689.

  • Cannon, B., M. Hermansson, S, Gyorke, P. Sommerharju, J.Virtanen, and K. H. Cheng. 2003. Regulation of calcium channel activity by lipid domain formation in Planar Lipid Bilayers. Biophysical Journal 85: 933-94

  • Z Du, N Colls, KH Cheng, MW Vaughn, and L Gollahon. 2006. Microfluidic-based diagnostics for cervical cancer cells. Biosens Bioelectron, 21: 1991-5

  • Swapnil P Wankhede, Zhiqiang Du, Jordan M Berg, Mark W Vaughn, Tim Dallas, Kwan H Cheng, and Lauren Gollahon. 2006. Cell Detachment Model for an Antibody-Based Microfluidic Cancer Screening System.Biotechnol Prog, 22: 1426-1433

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Research at the Tissue Level

Our research interests at the tissue level are focused on the use of magnetic resonance imaging to explore the physics of the relaxation and diffusion behavior of water in biological tissues, e.g., live human brain, havested animal tissues, tissue-like polymeric materials. We have looked at the MR relaxation and diffusion maps of various systems, especially the effect of hyperthemia on the damage of tissues in-vivo. Our most recent interests are in the creation and development of methodology and calibration protocol of 3D MR gel dosimetry for dose verification of advanced conformal radiation therapy currently used in cancer therapy. Results

Representative Publications
  • Cheng, K. H. and M. Hernandez. 1992. Magnetic resonance diffusion imaging detects structural damage in biological tissues upon hyperthermia. Cancer Research 52:6066-6073.

  • Cheng, K. H. 1993. Quantitation of non-Einstein diffusion behavior of water in biological tissues by proton MR diffusion imaging: Synthetic image calculations. Magnetic Resonance Imaging 11:569-58

  • Cheng, K. H. 1994. In vivo tissue characterization of human brain by chisquares parameter maps: Multiparameter proton T2-relaxation analysis. Magnetic Resonance Imaging 12:1099-1109.

  • Cardenas, R.L., K.H. Cheng, and K. Sack. 2001. The Effect of Cidofovir on Progressive Multifocal Leukoencephalopathy: An MRI Case Study. Neuroradialogy 43:379-382.

  • Cardenas, R. L., K. H. Cheng, L. J. Verhey, P. Xia, L. davis, and B. Cannon. 2002. A self consistent normalized calibration protocol for three dimensional magnetic resonance gel dosimetry. Magn. Reson. Imaging. 20: 667-679

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Research at the Human Level
Effect of Computer Technology on Student's Learning of Physics

Our research interests at the human level are focused on the use of Internet Technology to enhance undergraduate physics teaching. Currently, we are interested in evaluating the roles of on-line homework, web-based course tool (WebCT), Java Applets (Physlets) and digital video on the students' understanding of the concept of force and motion. We are also examining the gender difference in the effectiveness of Internet Technology.Results

Representative Publications
  • Cheng, K., B. A. Thacker, R. L. Cardenas, and C. Crouch.2004. Implementation of interactive online homework significantly enhances student's learning of physics concepts in an introductory physics course. American Journal of Physics 72: 1442-1453.  

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