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Research
In the body, tissues can be thought of as being made up of cells, a fluid phase, and the solid extracellular matrix that gives the tissue its form. Cells within a tissue can both generate and receive signals from molecules within their surrounding fluid as well as from the solid matrix support that they interact with. While the chemical signals provided by soluble molecules have been extensively studied, our understanding of the chemical and mechanical signals provided by the extracellular matrix has only begun to be elucidated. Dr. Sieminski investigates the impact changing the mechanical environment that cells sense, in combination with changing the biochemical environment, on cell behavior.
Three-dimensional cell-cell mechanical communication - The primary tool in this work is a three-dimensional model system of angiogenesis – the formation of new blood vessels. Understanding the effects of material properties, and how the stimulus they provide combine with other stimulus to direct cell behavior, has implications for not only fundamental cell biology, but also for cancer and the design of new biomaterials.
Preliminary data - Confocal microscope image stacks of endothelial cells ( fluorescently stained actin, in red, and nuclei, in blue/purple) within 3D collagen gels (in reflection, colored green) at 48 hours.
Publications
Biomaterial-Microvasculature Interactions. Sieminski AL and Gooch KJ. Biomaterials 2000; 21(22): 2232-41.
IGF-I and Mechanical Environment Interact to Modulate Engineered Cartilage Development. Gooch KJ, Blunk T, Courter DL, Sieminski AL, Bursac PM, Vunjak-Novakovic G, Freed LE. Biochem Biophys Res Commun 2001; 286 (5): 909-15.
Differential Effects of Growth Factors on Tissue-Engineered Cartilage. Blunk T, Sieminski AL, Gooch KJ, Courter DL, Hollander A, Nahir AM, Langer R, Vunjak-Novakovic G, and Freed LE. Tissue Engineering 2002; 8(1):73-84.
Bone Morphogenetic Proteins-2, -12, and –13 Modulate In Vitro Development of Engineered Cartilage. Gooch KJ, Blunk T, Courter DL, Sieminski AL, Vunjak-Novakovic G, Freed LE. Tissue Engineering 2002; 8(4): 591-601.
Systemic Delivery of hGH Using Genetically Modified Tissue-Engineered Microvascular Networks: Prolonged Delivery and Endothelial Survival with Inclusion of Non-Endothelial Cells. Sieminski AL, Padera RF, Blunk T, Gooch KJ. Tissue Engineering 2002; 8(6): 1057-1069.
Bone Morphogenetic Protein-9: A Potent Stimulant of Cartilage Development and Mineralization. Blunk T, Sieminski AL, Croft C, Courter DL, Chieh J, Khurana JS, and Gooch KJ. Growth Factor 2003; 21(2):71-8.
Salmon fibrin supports comparable sprout length, increased sprout number, and decreased degradation relative to human fibrin in an in vitro angiogenesis model. Sieminski AL and Gooch KJ. Journal of Biomaterials Science, Polymer Edition, 2004; 15(2): 237-42.
The Relative Magnitudes of Endothelial Force Generation and Matrix Stiffness Modulate Capillary Morphogenesis In Vitro. Sieminski AL, Hebbel, RP, and Gooch KJ. Experimental Cell Research, 2004; 297(2): 574-84.
Self-assembling short oligopeptides and the promotion of angiogenesis. Narmoneva DA, Oni O, Sieminski AL, Zhang S, Gertler JP, Kamm RD, Lee RT. Biomaterials, 2005; 26(23):4837-46.
Improved microvascular network in vitro by human blood outgrowth endothelial cells relative to vessel-derived endothelial cells. Sieminski AL, Hebbel RP, and Gooch KJ. Tissue Engineering 2005; 11(9-10): 1332-45.
Micropatterned Polymer Surfaces Improve Retention of Endothelial Cells Exposed to Flow-Induced Shear Stress. Daxini SC, Nichol JW, Sieminski AL, Smith G, Gooch KJ, Shastri VP. Biorheology. 2006; 43(1): 45-55.
Migration of tumor cells in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis. Zaman MH, Trapani LM, Sieminski A, Mackellar D, Gong H, Kamm RD, Wells A, Lauffenburger DA, Matsudaira P. PNAS 2006;103(29): 10889-94.
The Stiffness of Three-Dimensional Ionic Self-Assembling Peptide Gels Affects the Extent of Microvascular Network Formation. Sieminski AL, Was AS, Kim G, Kamm RD. Cell Biochem Biophys. 2007;49(2): 73-83.
Primary Sequence of Ionic Self-Assembling Peptide Gels Affects Endothelial Cell Adhesion and Capillary Morphogenesis. A.L. Sieminski, C.E. Semino, H. Gong, R.D. Kamm.Journal of Biomedical Materials Research 2008; 87(2):494-504.
Ena/VASP is Required for Endothelial Barrier Function In Vivo. C. Furman, A.L. Sieminski, A.V. Kwiatkowski, D. Rubinson, E. Vasile, R.T. Bronson, R. Fässler, and F.B. Gertler. Journal of Cell Biology 2007; 179(4): 761-75.
VASP involvement in force-mediated adherens junction strengthening. Kris AS, Kamm RD, Sieminski AL. Biochem Biophys Res Commun 2008; 375(1):134-8.
Pericellular conditions regulate extent of cell-mediated compaction of collagen gels. Stevenson MD, Sieminski AL, McLeod CM, Byfield FJ, Barocas VH, Gooch KJ. Biophys J. 2010 Jul 7;99(1):19-28.
Directed 3D cell alignment and elongation in microengineered hydrogels. Aubin H, Nichol JW, Hutson CB, Bae H, Sieminski AL, Cropek DM, Akhyari P, Khademhosseini A. Biomaterials. 2010 Sep;31(27):6941-6951.
Stability of a microvessel subject to structural adaptation of diameter and wall thickness. Shafer I, Nancollas R, Boes M, Sieminski AL, Geddes JB. Math Med Biol. 2010 Sep 24.
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