Ph.D. Applied Physics, California
Institute of Technology, 1995
Associate Professor of Bioengineering
231 Hallowell Bldg.
University Park, PA 16802
Tel: 814-865-8093
Fax: 814-865-0490
Email: aah12@psu.edu
Laboratory: Functional Imaging and Biophysics of Biological Systems
The research effort in our Laboratory for Functional Imaging
and Biophysics of Biological Systems focuses on understanding complex
biological processes (or systems) on a molecular-level. The following
three general themes describe well our research program.
- Energy Metabolism: Mitochondrion is the power plant that produces
most of the energy currencies (ATP) required for numerous cellular
functions. As a result, mitochondrial anomalies are linked to
a wide range of health problems that include loss of motor
control,
muscle weakness, poor growth, cardiac and liver diseases, diabetes,
seizures, and neurodegenerative diseases. We are interested in
using native biomolecules for studying energy metabolism in cells/tissues.
Of particular interest to us is to investigate mitochondrial
anomalies and metabolic activities by exploiting the fluorescence
of native
biomolecules (e.g., flavin, NADH) that are integral part of the
electron transport chain in the inner membrane of mitochondria.
- Protein-Protein Interaction and Protein Dynamics: Mechanisms
and pathways of protein folding have dominated the landscape
of experimental and theoretical biophysics for several decades.
The
reasons are that protein folding plays an important role in numerous
biological processes. Recent findings link abnormal protein folding
to a wide range of neurodegenerative diseases such as Parkinson's,
Alzheimer's and prion diseases. Furthermore, protein-protein
interactions and enzyme-catalyzed reactions underlie a vast
majority of biological
functions in living cells. Our interests in protein studies began
with intrinsically fluorescent proteins (IFPs), isolated from
jellyfish Aequorea victoria (GFPs) or Discosoma coral (DsRed).
In addition
to their interesting spectroscopy, dynamics and thermodynamics,
the genetic encoding of IFPs allows for site-specific and noninvasive
labeling of cells/organs for visualization of gene expression
and cellular functions. We are pursuing in-depth understanding
of the
structure-function relationship in proteins (i.e., GTP binding
proteins, LynB proteins, de novo purine biosynthesis pathway,
and molecular motors) on the single-molecule level.
- Specialized Domains in Biomembranes: Recent studies link specialized
domains “rafts” in plasma membranes to several cellular
functions (e.g., signal transduction and intracellular protein
trafficking), neurodegenerative diseases (e.g., Alzheimer’s
and prion), and virus budding (e.g., HIV). We are interested
in a real-time, quantitative investigation of the formation dynamics
and functions of these domains in both model systems and in vivo
membranes.
To achieve those goals, we are also interested in theoretical
modeling and technique development. Our biophotonics and biophysics
approaches
include noninvasive fluorescence microscopy and ultrafast laser
spectroscopy techniques with state-of-the-art technologies. We
are particularly interested in exploiting the sensitivity of
the excited-state dynamics and rotational mobility of biomolecules
to (1) their structure, (2) the surrounding environment and (3)
the biological state of cells/tissues. Such interdisciplinary
research
depends on students and postdoctoral associates from different
scientific backgrounds such as bioengineering, biology, chemistry
and physics.
Representative Publications
H.D. Vishwasrao, A.A. Heikal, K.A. Kasischke; W.W. Webb. Conformational
dependence of intracellular NADH on metabolic state revealed by
associated fluorescence anisotropy. J. Biol. Chem. Vol. 280(26):
25119-25126 (2005), Issue Cover and Paper of the Week.
Samuel T. Hess, Ahmed A. Heikal, and Watt W. Webb. Fluorescence
Photoconversion Kinetics in Novel Green Fluorescent Protein pH-Sensors
(pHluorins). J. Phys. Chem. (B) (2004), In Press. J. Korlach; D. Baird; A.A. Heikal; K.R. Gee; G.R. Hoffman; W.W.
Webb. Spontaneous nucleotide exchange in low molecular weight GTPases
by fluorescently labeled gamma-phosphate linked GTP analogs. .
Proc. Natl. Acad. Sci. U. S. A. (2003), 101(9), 2800-2805.
S.T. Hess; E.D. Sheets; A Wagenknecht-Wiesner; A.A. Heikal. Quantitative
analysis of the fluorescence properties of intrinsically fluorescent
proteins in living cells. Biophys. J. (2003), 85(4), 2566-2580.
A.A. Heikal; Webb W.W. Multiphoton fluorescence microscopy for
functional imaging of biomolecules. Trends in Optics and Photonics
(2002), 79 (Nonlinear Optics), 321-323.
S. Huang; A.A. Heikal; W.W. Webb. Two-photon fluorescence spectroscopy
and microscopy on NAD(P)H and flavoprotein. Biophys. J. (2002),
82(5), 2811-2825.
A.A. Heikal; S.T. Hess; E.D. Sheets; W.W. Webb. Mutation-photophysics
relationship in intrinsically fluorescent proteins. In “Femtochemistry
and Femtobiology: Ultrafast dynamics in molecular science”,
Editors: A. Douhal and J. Santamaria, World Scientific, Singapore,
(2002), Page 774-781.
S.T. Hess; S. Huang; A.A. Heikal; W.W. Webb. Biological and chemical
applications of fluorescence correlation spectroscopy: a review.
Biochem. (2002), 41(3), 697-705.
A.A. Heikal; S.T. Hess; W.W. Webb. Multiphoton spectroscopy and
excited state dynamics of enhanced green fluorescent protein (EGFP):
acid-base specificity. Chem. Phys. (2001), 274(1), 37-55.
A.A. Heikal; S.T. Hess; G.S. Baird; R.Y. Tsien; W.W. Webb. Molecular
spectroscopy and dynamics of intrinsically fluorescent proteins:
coral red (dsRed) and yellow (Citrine). Proc. Natl. Acad. Sci.
U. S. A. (2000), 97(22), 11996-12001.
P. Schwille; S. Kummer; A.A. Heikal; W.E. Moerner; W.W. Webb.
Fluorescence correlation spectroscopy reveals fast optical excitation-driven
intramolecular dynamics of yellow fluorescent proteins. Proc. Natl.
Acad. Sci. U. S. A. (2000), 97(1), 151-156.
Recent Publications from Heikal Laboratory
Florly S. Ariola, Deepti J. Mudaliar, Ronn P. Walvick, Ahmed A.
Heikal. 2006. Dynamics of lipid phases and lipid-marker interactions
in model biomembranes. Physical Chemistry Chemical Physics, 8(39):
4517-4529.
Kobin Shi, Ahmed A. Heikal, and Zhiwen Liu. 2006. A single-shot
approach for measuring two-photon action cross-section of fluorescent
markers. Optics Express, 14(19):8722-8727.
Yuexin Liu, Hye-Ryong Kim, Ahmed A. Heikal. 2006. Structural basis
of fluorescence fluctuation dynamics of green fluorescent proteins
in acidic environments. J. Phys. Chem. (B), JP062164T; In Press.
Davey, Angel M., Ronn P. Walvick, Yuexin Liu, Ahmed A. Heikal,
and Erin D. Sheets. 2006. Membrane order and molecular dynamics
associated with IgE receptor crosslinking in mast cells. Biophys.
J. BIOPHYSJ/2006/088815, In Press.
Yuexin Liu, Florly S. Ariola, Hye-Ryong Kim, Qianru Yu, Ronn P.
Walvick, and Ahmed A. Heikal. 2006. Two-photon excited-state and
conformation dynamics of NADH binding with dehydrogenases. Femtochemistry
and Femtobiology, VII, William Castlemann (Editor), Elsevier B.V.
Ltd. In Press.
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