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Matrix stiffness-modulated proliferation and secretory function of the airway smooth muscle cells.
Shkumatov, Artem,Thompson, Michael,Choi, Kyoung M,Sicard, Delphine,Baek, Kwanghyun,Kim, Dong Hyun,Tschumperlin, Daniel J,Prakash, Y S,Kong, Hyunjoon American Physiological Society 2015 American journal of physiology. Lung cellular and Vol.308 No.11
<P>Multiple pulmonary conditions are characterized by an abnormal misbalance between various tissue components, for example, an increase in the fibrous connective tissue and loss/increase in extracellular matrix proteins (ECM). Such tissue remodeling may adversely impact physiological function of airway smooth muscle cells (ASMCs) responsible for contraction of airways and release of a variety of bioactive molecules. However, few efforts have been made to understand the potentially significant impact of tissue remodeling on ASMCs. Therefore, this study reports how ASMCs respond to a change in mechanical stiffness of a matrix, to which ASMCs adhere because mechanical stiffness of the remodeled airways is often different from the physiological stiffness. Accordingly, using atomic force microscopy (AFM) measurements, we found that the elastic modulus of the mouse bronchus has an arithmetic mean of 23.1 ± 14 kPa (SD) (median 18.6 kPa). By culturing ASMCs on collagen-conjugated polyacrylamide hydrogels with controlled elastic moduli, we found that gels designed to be softer than average airway tissue significantly increased cellular secretion of vascular endothelial growth factor (VEGF). Conversely, gels stiffer than average airways stimulated cell proliferation, while reducing VEGF secretion and agonist-induced calcium responses of ASMCs. These dependencies of cellular activities on elastic modulus of the gel were correlated with changes in the expression of integrin-관1 and integrin-linked kinase (ILK). Overall, the results of this study demonstrate that changes in matrix mechanics alter cell proliferation, calcium signaling, and proangiogenic functions in ASMCs.</P>
Lee, Min Kyung,Rich, Max H.,Shkumatov, Artem,Jeong, Jae Hyun,Boppart, Marni D.,Bashir, Rashid,Gillette, Martha U.,Lee, Jonghwi,Kong, Hyunjoon Wiley (John WileySons) 2015 Advanced Healthcare Materials Vol.4 No.2
<P>This study demonstrates that a new method to align microparticles releasing bioactive molecules in microchannels of a hydrogel allows the guiding of growth direction and spacing of vascular networks.</P>
Smith, Cartney E.,Lee, JuYeon,Seo, Yongbeom,Clay, Nicholas,Park, Jooyeon,Shkumatov, Artem,Ernenwein, Dawn,Lai, Mei-Hsiu,Misra, Sanjay,Sing, Charles E.,Andrade, Brenda,Zimmerman, Steven C.,Kong, Hyunjo American Chemical Society 2017 ACS APPLIED MATERIALS & INTERFACES Vol.9 No.2
<P>Nanosized bioprobes that can highlight diseased tissue can be powerful diagnostic tools. However, a major unmet need is a tool with adequate adhesive properties and contrast-to-dose ratio. To this end, this study demonstrates that targeted superparamagnetic nanoprobes engineered to present a worm-like shape and hydrophilic packaging enhance both adhesion efficiency to target substrates and magnetic resonance (MR) sensitivity. These nanoprobes were prepared by the controlled self-assembly of superparamagnetic iron oxide nanoparticles (SPIONs) into worm-like superstructures using glycogen-like amphiphilic hyperbranched polyglycerols functionalized with peptides capable of binding to defective vasculature. The resulting worm-like SPION clusters presented binding affinity to the target substrate 10-fold higher than that of spherical ones and T<SUB>2</SUB> molar MR relaxivity 3.5-fold higher than that of conventional, single SPIONs. The design principles discovered for these nanoprobes should be applicable to a range of other diseases where improved diagnostics are needed.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/aamick/2017/aamick.2017.9.issue-2/acsami.6b10891/production/images/medium/am-2016-10891p_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/am6b10891'>ACS Electronic Supporting Info</A></P>