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The Lara Estroff Research Group |
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The Lara Estroff Research Group |
In order to understand how biomineralized tissues form, and to elucidate the structure/property relationships within these materials, we need to obtain high resolution images of both the structure and chemistry of these organic-inorganic composites. The Estroff Lab has helped to lead the advancement of state-of-the-art materials characterization techniques for revealing the internal, nanoscale structure of single crystal biominerals. We visualized, for the first time, the presence of organic aggregates within the single crystals that make up mollusk shells, and subsequently imaged the early stages of formation, revealing evidence of a particle-accretion pathway leading to the growth of crystallographically oriented tablets of nacre. To complete the structure-function analysis of these single-crystal composites, we measured a 60% increase in hardness of the calcite in mollusk shells as compared to geologic calcite, and contributed to a larger effort to model the origins of this hardening. More recently, we have interrogated the materials properties of pathological mineral deposits in tissues ranging from human breast tumors, to metastatic tumors in bone, to calcified aortic heart valves. These studies are some of the first to focus on the materials science of pathological mineralization, in contrast the biological approaches more commonly taken. These studies reveal the importance of multimodal imaging, including Raman microscopy, x-ray diffraction techniques, and electron microscopy, in enabling the description of heterogeneity in pathological mineral deposits that could not be seen by histology.
Boys, A.J.; Kunitake, J.A.M.R.; Henak, C.R.; Cohen, I.; Estroff, L.A.; Bonassar, L.J.; “Understanding the stiff-to-compliant transition of the meniscal attachments by spatial correlation of composition, structure, and mechanics” ACS Appl. Mater. Interfaces 2019, 11, 26559-26570. DOI: 10.1021/acsami.9b03595
Hovden, R.; Wolf, S.E.; Holtz, M.E.; Marin, F.; Muller, D.A.; Estroff, L.A.; “Nanoscale assembly processes revealed in the nacroprismatic transition zone of Pinna nobilis mollusk shells” Nat. Commun. 2015, 6, 1-7. DOI: 10.1038/ncomms10097
He, F.; Chiou, A.E.; Loh, H.C.; Lynch, M.; Seo, B.R.; Song, Y.H.; Lee, M.J.; Hoerth, R.; Bortel, E.L.; Willie, B.M.; Duda, G.N.; Estroff, L.A.; Masic, A.; Wagermaier, W.; Fratzl, P.; Fischbach, C.; “Multiscale characterization of the mineral phase at skeletal sites of breast cancer metastasis” Proc. Natl. Acad. Sci. 2017, 114, 10542-10547. DOI: 10.1073/pnas.1708161114
Chiou, A.E.; Hinckley, J.A.; Khaitan, R.; Varsano, N.; Wang, J.; Malarkey, H.F.; Hernandez, C.J.; Williams, R.M.; Estroff, L.A.; Weiner, S.; Addadi, L.; Wiesner, U.; Fischbach, C.; “Fluorescent silica nanoparticles to label metastatic tumor cells in mineralized bone microenvironments” Small 2021, 17, 2001432. DOI: 10.1002/smll.202001432
Richards, J.M.; Kunitake, J.A.M.R.; Hunt, H.B.; Wnorowski, A.N.; Lin, D.W.; Boskey, A.L.; Donnelly, E.; Estroff, L.A.; Butcher, J.T.; “Crystallinity of hydroxyapatite drives myofibroblastic activation and calcification in aortic valves” Acta biomater. 2018, 71, 24-36. DOI: 10.1016/j.actbio.2018.02.024
We apply our synthetic expertise to the design of in vitro systems to address questions about cell-mineral interactions, primarily in the context of disease. Our objective is to understand the biological role of the materials properties of mineral deposits in both healthy and diseased tissue. Our work in this area is distinguished by a focus on how the materials science of the system impacts the cellular response to the minerals. We have applied this approach to several different biological systems, specifically microcalcification formation in breast tumors and breast cancer metastasis to bone. For example, we are using a 3D cell culture model, which recapitulates key features of breast tumors, to investigate the biomineralization pathway(s) that lead(s) to the formation of microcalcifications in tumors. In related work, we have developed a suite of synthetic techniques to control the physicochemical properties of apatite crystals, including hydrothermal synthesis of well-defined nanoparticles and a biomimetic method for obtaining mineralized collagen fibrils. We have characterized how these materials interact with biomacromolecules to change their conformation and with cells to change their behavior. This body of work has provided important insight into how the materials properties of bone itself, rather than the cells, can provide microenvironmental cues to drive breast cancer metastasis to bone, and provides new targets for therapeutic strategies.
Choi, S.; Friedrichs, J.; Song, Y.H.; Werner, C.; Estroff, L.A.; Fischbach, C.; “Intrafibrillar, bone-mimetic collagen mineralization regulates breast cancer cell adhesion and migration” Biomaterials 2019, 198, 95-106. DOI: 10.1016/j.biomaterials.2018.05.002
Vidavsky, N.; Kunitake, J.A.M.R.; Chiou, A.; Northrup, P.A.; Porri, T.J.; Ling, L.; Fischbach, C.; Estroff, L.A.; “Studying biomineralization pathways in a 3D culture model of breast cancer microcalcifications” Biomaterials 2018, 179, 71-82. DOI: 10.1016/j.biomaterials.2018.06.030
Pathi, S.P.; Lin, D.W.; Dorvee, J.R.; Estroff, L.A.; Fischbach-Teschl, C.; “Hydroxyapatite nanoparticle-containing scaffolds for the study of breast cancer bone metastasis” Biomaterials 2011, 32, 5112-5122. DOI: 10.1016/j.biomaterials.2011.03.055
He, F.; Springer, N.L.; Whitman, M.A.; Pathi, S.P.; Lee, Y.; Monahan, S.; Marcott, S.; Chiou, A.E.; Blank, B.S.; Iyengar, N.; Morris, P.G.; Jochelson, M.; Hudis, C.A.; Shah, P.; Kunitake, J.A.M.R.; Estroff, L.A.; Lammerding, J.; Fischbach, C.; “Hydroxyapatite mineral enhances malignant potential in a tissue-engineered model of ductal carcinoma in situ (DCIS)” Biomaterials 2019, 224, 119489. DOI: 10.1016/j.biomaterials.2019.119489
Vidavsky, N.; Kunitake, J.A.M.R.; Estroff, L.A.; “Multiple pathways for pathological calcification in the human body” Adv. Healthc. Mater. 2021, 10, 2001271.DOI: 10.1002/adhm.202001271
Kunitake, J.A.M.R.; Choi, S.; Nguyen, K.X.; Lee, M.M.; He, F.; Sudilovsky, D.; Morris, P.G.; Jochelson, M.S.; Hudis, C.A.; Muller, D.A.; Fratzl, P.; Fischbach, C.; Masic, A.; Estroff, L.A.; “Correlative imaging reveals physioloical heterogeneity of microcalcifications in human breast carcinomas” J. Struct. Biol. 2018, 202, 25-34. DOI: 10.1016/j.jsb.2017.12.002
Vidavsky, N.; Kunitake, J.A.M.R.; Diaz-Rubio, M.E.; Chiou, A.E.; Loh, H.-C.; Zhang, S.; Masic, A.; Fischbach, C.; Estroff, L.A.; “Mapping and profiling lipid distribution in a 3D model of breast cancer progression” ACS Cent. Sci. 2019, 5, 768-780. DOI: 10.1021/acscentsci.8b00932
The Estroff Lab has advanced the field of bio-inspired crystal growth in which we learn new tricks from biology and apply them to synthetic systems. We have significantly contributed to the field's understanding of the mechanisms by which biological and synthetic crystals occlude additives ranging from small molecules to gel fibers to nanoparticles, and the effect of these additives on the materials properties of the resulting complex crystalline structures. We have developed multiple bio-informed synthetic strategies to grow complex crystals with a variety of inclusions and properties. We have focused on crystal growth in hydrogels as an approach for preparing gel/single-crystal composites. Importantly, we demonstrated that gel-grown crystals can incorporate the gel matrix to form crystalline materials reminiscent of biogenic single-crystal composites. More recently, we have expanded our tool-box to include crystal growth in confinement as a means to promote inclusion of second-phase particles, e.g., incorporation of plasmonic nanoparticles within semiconductor rods. Very recently, we have introduced a nanostructured block-copolymer based template (iSTAMP) to direct the crystallization of materials. We can change, in a controlled fashion, the nanoscale geometry, topology and surface chemistry of this template, thus enabling us to explore the connection between chemical functionality and topology in directing nucleation and growth. This powerful new platform can interrogate information transfer between the organic and inorganic components during the early stages of crystallization.
Palin, D.; Style, R.W.; Zlopaša, J.; Petrozzini, J.J.; Pfeifer, M.A.; Jonkers, H.M.; Dufresne, E.R.; Estroff, L.A.; “Forming anisotropic crystal composites: Assessing the mechanical translation of gel network anisotropy to calcite crystal form” J. Am. Chem. Soc. 2021, 143, 3439-3447. DOI: 10.1021/jacs.0c12326
Asenath-Smith, E.; Li, H.; Keene, E.C.; Seh, Z.W.; Estroff, L.A.; “Crystal growth of calcium carbonate in hydrogels as a model of biomineralization” Adv. Func. Mater. 2012, 22, 2891-2914. DOI: 10.1002/adfm.201200300
Li, H. Y.; Xin, H. L.; Muller, D. A.; Estroff, L. A.; “Visualizing the 3D internal structure of calcite single crystals grown in agarose hydrogels” Science 2009, 326, 1244-1247. DOI: 10.1126/science.1178583
Oleske, K.W.; Barteau, K.P.; Beaucage, P.A.; Asenath-Smith, E.; Wiesner, U.; Estroff, L.A.; “Nanopatterning of crystalline transition metal oxides by surface templated nucleation on block copolymer mesostructures” Cryst. Growth Des. 2017, 17, 5775-5782. DOI: 10.1021/acs.cgd.7b00767
We apply our understanding of biomineralization to designing tissue engineering strategies for gradient tissues such as the bone-cartilage and bone-meniscus interface. We have performed correlative chemical, structural, and mechanical analysis of the stiff-to-compliant gradient in the meniscus-to-bone enthesis. The results of this study in turn inform the design of tissue engineered constructs of similar mechanically robust interfaces. Ultimately, these efforts can lead to implantable materials for the repair of damaged interfacial tissues in the body.
Boys, A.J.; Kunitake, J.A.M.R.; Henak, C.R.; Cohen, I.; Estroff, L.A.; Bonassar, L.J.; “Understanding the stiff-to-compliant transition of the meniscal attachments by spatial correlation of composition, structure, and mechanics” ACS Appl. Mater. Interfaces 2019, 11, 26559-26570. DOI: 10.1021/acsami.9b03595
Zhou, H.; Boys, A.J.; Harrod, J.B.; Bonassar, L.J.; Estroff, L.A.; “Mineral distribution spatially patterns bone marrow stromal cell behavior on monolithic bone scaffolds” Acta biomater. 2020, 112, 274-285. DOI: 10.1016/j.actbio.2020.05.032
Iannucci, L.E.; Boys, A.J.; McCorry, M.C.; Estroff, L.A.; Bonassar, L.J.; “Cellular and chemical gradients to engineer the meniscus-to-bone insertion” Adv. Healthc. Mater. 2019, 8, 1800806. DOI: 10.1002/adhm.201800806
Boys, A.J.; McCorry, M.C.; Rodeo, S.; Bonassar, L.J.; Estroff, L.A.; “Next generation tissue engineering of orthopedic soft tissue-to-bone interfaces” MRS Commun. 2017, 7, 289-308. DOI: 10.1557/mrc.2017.91
