TY - JOUR A1 - Frey, Christoph A1 - Sales, Adria A1 - Athanasopulu, Kiriaki A1 - Spatz, Joachim A1 - Kemkemer, Ralf T1 - Hydrogels with precisely nano-functionalized micro-topography for cell guidance JF - Biomedizinische Technik / Biomedical engineering N2 - In vivo, cells encounter different physical and chemical signals in the extracellular matrix (ECM) which regulate their behavior. Examples of these signals are micro- and nanometer-sized features, the rigidity, and the chemical composition of the ECM. The study of cell responses to such cues is important to understand complex cell functions, some diseases, and is basis for the development of new biomaterials for applications in medical implants or regenerative medicine. Therefore, the development of new methods for surface modifications with controlled physical and chemical features is crucial. In this work, we report a new combination of micelle nanolithography (BCML) and soft micro-lithography, for the production of polyethylene glycol (PEG) hydrogels, with a micro-grooved surface and decoration with hexagonally precisely arranged gold nanoparticles (AU NPs). The Au-NPs are used for binding adhesive ligands in a well-defined density. First tests were performed by culturing human fibroblasts on the gels. Adhesion and alignment of the cells along the parallel grooves of the surface were investigated. The substrates could provide a new platform for studying cell contact guidance by micro structures, and may enable a more precise control of cell behavior by nanometrically controlled surface functionalization. Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bsz:rt2-opus4-755 SN - 0013-5585 VL - 59 IS - s1 : Track A - Biomaterials and Biocompatibility SP - S6 EP - S9 PB - de Gruyter CY - Berlin ER - TY - JOUR A1 - Greiner, Alexandra A1 - Hoffmann, Peter A1 - Bruellhoff, Kristina A1 - Jungbauer, Simon A1 - Spatz, Joachim A1 - Moeller, Martin A1 - Kemkemer, Ralf A1 - Groll, Jürgen T1 - Stable biochemically micro-patterned hydrogel layers control specific cell adhesion and allow long term cyclic tensile strain experiments JF - Macromolecular bioscience N2 - Poly(dimethylsiloxane) can be covalently coated with ultrathin NCO-sP(EO-stat-PO) hydrogel layers which permit covalent binding of cell adhesive moieties, while minimizing unspecific cell adhesion on non-functionalized areas. We applied long term uniaxial cyclic tensile strain (CTS) and revealed (a) the preservation of protein and cell-repellent properties of the NCO-sP(EO-stat-PO) coating and (b) the stability and bioactivity of a covalently bound fibronectin (FN) line pattern. We studied the adhesion of human dermal fibroblast (HDFs) on non-modified NCO-sP(EO-stat-PO) coatings and on the FN. HDFs adhered to FN and oriented their cell bodies and actin fibers along the FN lines independently of the direction of CTS. This mechanical long term stability of the bioactive, patterned surface allows unraveling biomechanical stimuli for cellular signaling and behavior to understand physiological and pathological cell phenomenon. Additionally, it allows for the application in wound healing assays, tissue engineering, and implant development demanding spatial control over specific cell adhesion. KW - hydrogels KW - mechanical properties KW - micro-contact printing of fibronectin KW - specific cell adhesion KW - spin coating of star polymers Y1 - 2015 U6 - http://dx.doi.org/10.1002/mabi.201400261 SN - 1616-5187 VL - 14 IS - 11 SP - 1547 EP - 1555 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Mills, Kristen A1 - Kemkemer, Ralf A1 - Rudraraju, Shiva A1 - Garikipati, Krishna T1 - Elastic free energy drives the shape of prevascular solid tumors JF - PLoS one N2 - It is well established that the mechanical environment influences cell functions in health and disease. Here, we address how the mechanical environment influences tumor growth, in particular, the shape of solid tumors. In an in vitro tumor model, which isolates mechanical interactions between cancer tumor cells and a hydrogel, we find that tumors grow as ellipsoids, resembling the same, oft-reported observation of in vivo tumors. Specifically, an oblate ellipsoidal tumor shape robustly occurs when the tumors grow in hydrogels that are stiffer than the tumors, but when they grow in more compliant hydrogels they remain closer to spherical in shape. Using large scale, nonlinear elasticity computations we Show that the oblate ellipsoidal shape minimizes the elastic free energy of the tumor-hydrogel system. Having eliminated a number of other candidate explanations, we hypothesize that minimization of the elastic free energy is the reason for predominance of the experimentally observed ellipsoidal shape. This result may hold significance for explaining the shape progressio. Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bsz:rt2-opus4-780 SN - 1932-6203 VL - 9 IS - 7 SP - 1 EP - 7 PB - PLoS CY - Lawrence, Kanada ER - TY - JOUR A1 - Nisenholz, Noam A1 - Rajendran, Kavitha A1 - Dang, Quynh A1 - Chen, Hao A1 - Kemkemer, Ralf A1 - Krishnan, Ramaswamy A1 - Zemel, Assaf T1 - Active mechanics and dynamics of cell spreading on elastic substrates JF - Soft matter N2 - The spreading area of cells has been shown to play a central role in the determination of cell fate and tissue morphogenesis; however, a clear understanding of how spread cell area is determined is still lacking. The observation that cell area and force generally increase with substrate rigidity suggests that cell area is dictated mechanically, by means of a force-balance between the cell and the substrate. A simple mechanical model, corroborated by experimental measurements of cell area and force is presented to analyze the temporal force balance between the cell and the substrate during spreading. The cell is modeled as a thin elastic disc that is actively pulled by lamellipodia protrusions at the cell front. The essential molecular mechanisms of the motor activity at the cell front, including, actin polymerization, adhesion kinetics, and the actin retrograde flow, are accounted for and used to predict the dynamics of cell spreading on elastic substrates; simple, closed-form expressions for the evolution of cell size and force are derived. Time-resolved, traction force microscopy, combined with measurements of cell area are performed to investigate the simultaneous variations of cell size and force. We find that cell area and force increase simultaneously during spreading but the force develops with an apparent delay relative to the increase in cell area. We demonstrate that this may reflect the strain-stiffening property of the cytoskeleton. We further demonstrate that the radial cell force is a concave function of spreading speed and that this may reflect the strengthening of cell–substrate adhesions during spreading. Y1 - 2015 U6 - http://dx.doi.org/10.1039/C4SM00780H SN - 1744-683X VL - 10 IS - 37 SP - 7234 EP - 7246 PB - Royal Society of Chemistry CY - London ER - TY - JOUR A1 - Sales, Adria A1 - Wang, Fanlu A1 - Chen, Hao A1 - Kemkemer, Ralf A1 - Greiner, Alexandra T1 - Cell-age and cell type-dependent behavior of human vascular cells on micro-structured or soft polymer substrates JF - Biomedizinische Technik / Biomedical Engineering N2 - Increasing number of studies are focused on how adherent cells respond, in vitro, to different properties of a material. Typical properties are the surface chemistry, topographical cues (at the nano- and micro-scale) of the surface, and the substrate stiffness. Cell Response studies are of importance for designing new biomaterials with applications in cell culture technologies, regenerative medicine, or for medical implants. However, only very few studies take the cell age factor, respectively the donor age, into account. In this work, we tested two types of human vascular cells (smooth muscle and endothelial cells) from old and young donors on (a) micro-structured surfaces made of pol (dimethylsiloxane) or on (b) flat polyacrylamide hydrogels with varying stiffnesses. These experiments reveal age-dependent and cell typedependent differences in the cell response to the topography and stiffness, and may establish the Basis for further studies focusing on cell age-dependent responses. Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bsz:rt2-opus4-801 SN - 1862-278X VL - 59 IS - s1 : Track D - Cellular, Tissue and Bioengineering SP - S286 EP - S289 PB - de Gruyter CY - Berlin ER - TY - JOUR A1 - Greiner, Alexandra A1 - Biela, Sarah A1 - Chen, Hao A1 - Spatz, Joachim A1 - Kemkemer, Ralf T1 - Temporal responses of human endothelial and smooth muscle cells exposed to uniaxial cyclic tensile strain JF - Experimental biology and medicine N2 - The physiology of vascular cells depends on stimulating mechanical forces caused by pulsatile flow. Thus, mechano-transduction processes and responses of primary human endothelial cells (ECs) and smooth muscle cells (SMCs) have been studied to reveal cell-type specific differences which may contribute to vascular tissue integrity. Here, we investigate the dynamic reorientation response of ECs and SMCs cultured on elastic membranes over a range of stretch frequencies from 0.01 to 1 Hz. ECs and SMCs show different cell shape adaptation responses (reorientation) dependent on the frequency. ECs reveal a specific threshold frequency (0.01 Hz) below which no responses is detectable while the threshold frequency for SMCs could not be determined and is speculated to be above 1 Hz. Interestingly, the reorganization of the actin cytoskeleton and focal adhesions system, as well as changes in the focal adhesion area, can be observed for both cell types and is dependent on the frequency. RhoA and Rac1 activities are increased for ECs but not for SMCs upon application of a uniaxial cyclic tensile strain. Analysis of membrane protrusions revealed that the spatial protrusion activity of ECs and SMCs is independent of the application of a uniaxial cyclic tensile strain of 1 Hz while the total number of protrusions is increased for ECs only. Our study indicates differences in the reorientation response and the reaction times of the two cell types in dependence of the stretching frequency, with matching data for actin cytoskeleton, focal adhesion realignment, RhoA/Rac1 activities, and membrane protrusion activity. These are promising results which may allow cell-type specific activation of vascular cells by frequency selective mechanical stretching. This specific activation of different vascular cell types might be helpful in improving strategies in regenerative medicine. KW - smooth muscle cell KW - endothelial cell KW - uniaxial cyclic tensile strain KW - actin KW - focal adhesion KW - Rho GTPases Y1 - 2015 U6 - http://dx.doi.org/10.1177/1535370215570191 SN - 0037-9727 VL - 240 IS - 10 SP - 1298 EP - 1309 PB - Sage CY - London ER - TY - CHAP A1 - Zemel, Assaf A1 - Kemkemer, Ralf ED - Kaunas, Roland T1 - Cell-matrix and cell-cell mechanical interactions T2 - Cell and matrix mechanics Y1 - 2015 SN - 978-1-4665-5381-1 SP - 119 EP - 148 PB - CRC Press CY - Boca Raton ER - TY - CHAP A1 - Mills, Kristen A1 - Rudraraju, Shiva A1 - Kemkemer, Ralf A1 - Garikipati, Krishna ED - Kaunas, Roland T1 - Continuum physics of tumor growth T2 - Cell and matrix mechanics N2 - Continuum physics modeling of tumor growth is a rich topic with room for rather sophisticated models of reaction-transport and mechanics. It also has the attraction of being able to pose and examine solutions to certain questions on tumor growth that are difficult to access using experimental methods alone. However, the imperative of experimental biophysical investigations cannot by understated. Y1 - 2015 SN - 978-1-4665-5381-1 SP - 309 EP - 328 PB - CRC Press CY - Boca Raton ER - TY - JOUR A1 - Gittel, Bianca A1 - Kemkemer, Ralf A1 - Krastev, Rumen A1 - Athanasopulu, Kiriaki A1 - Rudt, Alexander T1 - Modification of polyelectrolyte multilayer coatings using nanoparticles to optimize adhesion and proliferation of different cell types JF - Bionanomaterials : journal of functional materials, biomechanics, and tissue engineering N2 - Adapting characteristics of biomaterials specifically for in vitro and in vivo applications is becoming increasingly important in order to control interactions between material and biological systems. These complex interactions are influenced by surface properties like chemical composition, charge, mechanical and topographic attributes. In many cases it is not useful or even not possible to alter the base material but changing surface, to improve biocompatibility or to make surfaces bioactive, may be achieved by thin coatings. An already established method is the coating with polyelectrolyte multilayers (PEM). To adjust adhesion, proliferation and improve vitality of certain cell types, we modified the roughness of PEM coatings. We included different types nanoparticles (NP’s) in different concentrations into PEM coatings for controlling surface roughness. Surface properties were characterized and the reaction of 3 different cell types on these coatings was tested. Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bsz:rt2-opus4-13329 SN - 2193-0651 VL - 17 IS - S1 SP - 123 PB - De Gruyter CY - Berlin ER - TY - JOUR A1 - Athanasopulu, Kiriaki A1 - Kemkemer, Ralf A1 - Lorenz, Günter A1 - Kutuzova, Larysa T1 - Functionalization of PU-based materials for orthopedic applications JF - Bionanomaterials : journal of functional materials, biomechanics, and tissue engineering N2 - Knee osteoarthritis is a common complication and can lead to total loss of joint function in patients. Treatment by either partial or total knee replacement with appropriate UHMWPE based implantsis highly invasive, may cause complications and may show unsatisfying results. Alternatively, treatment may be done by insertion of an elastic interpositional knee spacer with optimized material characteristics. We report the development of high performance polyurethane-based polymers modified with bioactive molecules for fabrication of such knee spacers. In order to tailor mechanical and tribological properties and to improve resist to enzymatic degradation we propose a core-shell model for the spacer with specifically adapted properties. Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bsz:rt2-opus4-13332 SN - 2193-066X VL - 17 IS - S1 SP - 158 PB - De Gruyter CY - Berlin ER -