Helen M. Buettner
Associate Professor &
|The development of strategies
for reversing the debilitating effects of nerve injury and disease currently
hinges on a better understanding of mechanisms by which the neural circuitry
is established and maintained in the healthy animal.
At the cellular level, neurons form connections by extending axons and dendrites (referred to collectively as neurites) from the cell body to appropriate innervation targets. The leading tip of a growing neurite terminates in a flattened, motile structure called the growth cone which resembles a motile cell both in morphology and dynamic activity. Neurite extension proceeds along the path of growth cone movement; thus, the motile behavior of the growth cone represents a primary factor in determining the ultimate pattern of neuronal connections in the nervous system. In the course of quantitating the effects of growth cone motility on neuronal pattern formation, we have begun to address the following issues.
Filopodial Dynamics. Growth cones display fine projections called filopodia around their periphery that continually extend and retract as the growth cone avances over the substrate. This behavior is often interpreted as "sampling" of the substrate: receptors on the filopodia interact with the substrate, providing directional information that guides the growth cone toward favorable conditions, for example, towards more adhesive regions of the substrate. Dynamic data on the kinetics of filopodial extension, retraction, and turnover are being obtained by high resolution video microscopy to provide information for developing a mathematical description of this sensing activity. This description is, in turn, being applied to model the substrate guidance of growth cone motility.
Growth Cone Guidance. To study the growth
cone response to substrate guidancecues, we are employing microelectronics
techniques to create precise patterns of guidance molecules on a substrate
and growth cone behavior in this environment using videomicroscopy. Questions
of interest include the effects of varying the affinity, surface concentration
and identity of the guidance molecule, the geometrical pattern in which
the regions of guidance molecule are placed, and the size of the these
regions relative to the growth cone dimensions. The biophysical interactions
at substrate borders leading to directional movement are being investigated
by hypothesizing mechanisms for changes in the motile response at the
border and incorporating these into a mathematical model that accounts
for deviations from the behavior observed on a homogeneous substrate.
Odde, D.J. and Buettner, H.M. (1995), Time Series Characterization of Simulated Microtubule Dynamics in the Nerve Growth Cone, Ann. Biomed. Eng. 23: 268-286.
Buettner, H.M. (1995), Neuroengineering in Biological and Biosynthetic Systems, Curr. Op. Biotechnology 6: 225-229.
Riley, M.R., Buettner, H.M., Muzzio, F.M., Reyes, S.C. (1995), Monte Carlo Simulation of Diffusion and Reaction in Two-Dimensional Cell Structures, Biophys. J. 68: 1716-1726,
Buettner, H.M. (1994). Nerve Growth Dynamics: Quantitative Models for Nerve Development and Regeneration, Ann. N.Y. Acad.Sci. 745: 210-221
Buettner, H.M. (1995). Computer Simulation of Nerve Growth Cone Filopodial Dynamics for Visualization and Analysis, Cell Motil. Cytoskel., in press.
Odde, D.J. , Cassimeris, L., Buettner, H.M. (1995), Spectral Analysis of Microtubule Assembly Dynamics, AIChE J, in press.
Odde, D.J. , Cassimeris, L., Buettner, H.M. (1995), Kinetics of Microtubule Catastrophe Assessed by Probabilistic Analysis, Biophys. J., in press.