1. Bioinspired, Non-Covalent Assembly of
Materials:
Stem cell
activities, including self-renewal and
differentiation, are strongly influenced by signals
present in their microenvironment. Our group is
using novel materials chemistry to control the
signals present in the local stem cell microenvironment.
Our approaches use non-covalent interactions between
biological molecules (e.g. proteins, DNA strands) to
assemble signaling complexes on cell culture
substrates and within extracellular matrices. These
non-covalent assembly approaches are being used to
understand/control stem cell differentiation and as
a mechanism for targeted drug delivery.
W.L. Murphy, K.O. Mercurius and M.
Mrksich. Active site-directed immobilization of a
protein domain to mediate cell adhesion. Langmuir,
2004, 20, 1026-1030.
S.Y. Choi, W.L. Murphy.
Multifunctional mixed SAMs that promote both cell
adhesion and non-covalent DNA immobilization,
Langmuir,2008; 24:6873-6880.
G.A. Hudalla, W.L. Murphy.
Non-covalent Assembly of Peptide-Growth Factor
Complexes to Spatially Control Cell Activity.
American Chemical Society PMSE preprints,
2008.
2. Creation of Nanostructured, Bio-Functional
Materials
Biological macromolecules, including
proteins and poly(nucleotides), provide the most
basic unit of function in living systems. For
example, proteins fold to give structurally
well-defined three-dimensional macromolecules and in
many cases undergo highly complex changes in
response to a broad spectrum of environmental cues,
including light, pH, and the binding of biological
ligands. Inspired by these examples from biology, we
are creating synthetic materials that have
macroscopic properties that derive from the
nanometer-scale properties of their component
building blocks. The building blocks we are exploring
include engineered proteins, synthetic peptides, and
DNA strands.
W.L.
Murphy, W.S. Dillmore, J. Modica, M. Mrksich.
Dynamic Hydrogels: Translating a Protein
Conformational Change into Macroscopic Motion.
Angewandte Chemie Int. Ed., 2007;46:3066-3069.
Z. Sui, W.J. King, W.L.
Murphy. Dynamic materials based on a protein
conformational change. Advanced Materials,
2007;19:3377-3380.
Z. Sui, W.J. King, W.L.
Murphy. Protein-based hydrogels with tunable dynamic
responses, Advanced Functional Materials, 2008;18:1824-1831.
3. Templated Assembly of
Biomaterials:
Natural synthesis of materials is
often a templated, multi-step process that produces tissues and organs with heterogeneous
properties. As a result, biological materials have
mechanical and biochemical properties that are
tailored to a specific location in the body. In
addition, biological materials (e.g. growth factors)
often appear and disappear in a timed manner during development of an organism.
Using natural assembly processes as an inspiration,
we are developing approaches for templated assembly
of synthetic biomaterials. The ultimate goal of
these efforts is to control the physical and/or
biochemical properties of a material, which can then
be used for stem cell culture, regenerative medicine applications, and
medical device design.
W.L. Murphy and D.J. Mooney.
Bioinspired synthesis of crystalline carbonated
apatite on biodegradable polymer substrata. Journal
of the American Chemical Society, 2002,
124, 1910-1917.
W.L. Murphy C.A. Simmons, D. Kaigler
and D.J. Mooney. Engineering bone regeneration via
biomineral presentation and induced angiogenesis.
Journal of Dental Research, 2004, 83,
204-210.
4. Assembly of Biomaterial
Platforms for Stem Cell Screening:
The
complexity of stem cell differentiation and tissue
development often require multiple types of signals
to be present in distinct locations on a cell
culture substrate or within an extracellular
matrix. The distribution of signals in the
extracellular microenvironment is influenced by both the
type of molecule that is introduced into the
environment, and the diffusion of molecules to and
from cells. We are developing approaches that aim to
control location and diffusion of biological
molecules (e.g. proteins, DNA strands) in materials, with the
ultimate goal of generating tailored signaling
environments. These
approaches are inspired by the mechanisms that
control natural development of tissues, and are
aimed toward understanding and re-creating natural
developmental processes..
G. Hudalla, T.S. Eng, W.L. Murphy.
An approach to modulate degradation and mesenchymal
stem cell behavior in poly(ethylene glycol)
networks, Biomacromolecules, 2008; 9:842-849.
L. Jongpaiboonkit, W.J.
King, G.E. Lyons, A. Paguirigan, J. Warrick, D.J.
Beebe, W.L. Murphy, Adaptable hydrogel array format
for 3-dimensional cell culture, Biomaterials,
2008;29:3346-3356.
L.
Jongpaiboonkit, W.J. King, W.L. Murphy. Screening
for 3-D environments that support human mesenchymal
stem cell viability using hydrogel arrays, Tissue
Engineering, In Press, 2008.
B.J. Peret, W.L. Murphy.
Controllable Formation Soluble Protein Concentration
Gradients in Hydrogels, Advanced Functional
Materials, In Press, 2008.
