scholarly journals Mechanical intercellular communication via matrix-borne cell force transmission during vascular network formation

2021 ◽  
Author(s):  
Christopher D Davidson ◽  
Samuel J DePalma ◽  
William Y Wang ◽  
Jordan L Kamen ◽  
Danica Kristen P Jayco ◽  
...  

Intercellular communication is critical to the development and homeostatic function of all tissues. Previous work has shown that cells can communicate mechanically via transmission of cell-generated forces through their surrounding extracellular matrix, but this process is not well understood. Here, we utilized synthetic, electrospun fibrous matrices in conjunction with a microfabrication-based cell patterning approach to examine mechanical intercellular communication (MIC) between endothelial cells (ECs) during the assembly of microvascular networks. We found that cell force-mediated matrix displacements in deformable fibrous matrices underly directional migration of neighboring ECs towards each other prior to the formation of stable cell-cell connections. We also identified a critical role for intracellular calcium signaling mediated by focal adhesion kinase and TRPV4 during MIC that extends to multicellular assembly of vessel-like networks in 3D fibrin hydrogels. The results presented here are critical to the design of biomaterials that support cellular self-assembly for tissue engineering applications.

2020 ◽  
Vol 142 (11) ◽  
Author(s):  
Christopher D. Davidson ◽  
Danica Kristen P. Jayco ◽  
William Y. Wang ◽  
Ariella Shikanov ◽  
Brendon M. Baker

Abstract Mechanical interactions between cells and their surrounding extracellular matrix (ECM) guide many fundamental cell behaviors. Native connective tissue consists of highly organized, 3D networks of ECM fibers with complex, nonlinear mechanical properties. The most abundant stromal matrix component is fibrillar type I collagen, which often possesses a wavy, crimped morphology that confers strain- and load-dependent nonlinear mechanical behavior. Here, we established a new and simple method for engineering electrospun fibrous matrices composed of dextran vinyl sulfone (DexVS) with controllable crimped structure. A hydrophilic peptide was functionalized to DexVS matrices to trigger swelling of individual hydrogel fibers, resulting in crimped microstructure due to the fixed anchorage of fibers. Mechanical characterization of these matrices under tension confirmed orthogonal control over nonlinear stress–strain responses and matrix stiffness. We next examined ECM mechanosensing of individual endothelial cells (ECs) and found that fiber crimp promoted physical matrix remodeling alongside decreases in cell spreading, focal adhesion area, and nuclear localization of Yes-associated protein (YAP). These changes corresponded to an increase in migration speed, along with evidence for long-range interactions between neighboring cells in crimped matrices. Interestingly, when ECs were seeded at high density in crimped matrices, capillary-like networks rapidly assembled and contained tube-like cellular structures wrapped around bundles of synthetic matrix fibers due to increased physical reorganization of matrix fibers. Our work provides an additional level of mechanical and architectural tunability to synthetic fibrous matrices and implicates a critical role for mechanical nonlinearity in EC mechanosensing and network formation.


Langmuir ◽  
2006 ◽  
Vol 22 (22) ◽  
pp. 9260-9263 ◽  
Author(s):  
Atsumi Wakabayashi ◽  
Yuki Sasakawa ◽  
Toshiaki Dobashi ◽  
Takao Yamamoto

2016 ◽  
Vol 60 (4) ◽  
pp. 2435-2442 ◽  
Author(s):  
Tecla Ciociola ◽  
Thelma A. Pertinhez ◽  
Laura Giovati ◽  
Martina Sperindè ◽  
Walter Magliani ◽  
...  

ABSTRACTSynthetic peptides encompassing sequences related to the complementarity-determining regions of antibodies or derived from their constant region (Fc peptides) were proven to exert differential antimicrobial, antiviral, antitumor, and/or immunomodulatory activitiesin vitroand/orin vivo, regardless of the specificity and isotype of the parental antibody. Alanine substitution derivatives of these peptides exhibited unaltered, increased, or decreased candidacidal activitiesin vitro. The bioactive IgG-derived Fc N10K peptide (NQVSLTCLVK) spontaneously self-assembles, a feature previously recognized as relevant for the therapeutic activity of another antibody-derived peptide. We evaluated the contribution of each residue to the peptide self-assembling capability by circular-dichroism spectroscopy. The interaction of the N10K peptide and its derivatives withCandida albicanscells was studied by confocal, transmission, and scanning electron microscopy. The apoptosis and autophagy induction profiles in yeast cells treated with the peptides were evaluated by flow cytometry, and the therapeutic efficacy against candidal infection was studied in aGalleria mellonellamodel. Overall, the results indicate a critical role for some residues in the self-assembly process and a correlation of that capability with the candidacidal activities of the peptidesin vitroand their therapeutic effectsin vivo.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Karen E. Marshall ◽  
Devkee M. Vadukul ◽  
Liza Dahal ◽  
Alina Theisen ◽  
Milena W. Fowler ◽  
...  
Keyword(s):  

2020 ◽  
Vol 52 (8) ◽  
pp. 923-930 ◽  
Author(s):  
Hanae Arakawa ◽  
Kumi Takeda ◽  
Sayuri L. Higashi ◽  
Aya Shibata ◽  
Yoshiaki Kitamura ◽  
...  

AbstractVarious biofunctional hydrogel materials can be fabricated in aqueous media through the self-assembly of peptide derivatives, forming supramolecular nanostructures and their three-dimensional networks. In this study, we describe the self-assembly of new Fmoc-dipeptides comprising α-methyl-L-phenylalanine. We found that the position and number of methyl groups introduced onto the α carbons of the Fmoc-dipeptides by α-methyl-L-phenylalanine have a marked influence on the morphology of the supramolecular nanostructure as well as the hydrogel (network) formation ability.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1208
Author(s):  
Narsimha Mamidi ◽  
Ramiro Velasco Delgadillo ◽  
Aldo Gonzáles Ortiz ◽  
Enrique Barrera

Herein, poly (N-(4-aminophenyl) methacrylamide))-carbon nano-onions (PAPMA-CNOs = f-CNOs) and anilinated-poly (ether ether ketone) (AN-PEEK) have synthesized, and AN-PEEK/f-CNOs composite thin films were primed via layer-by-layer (LbL) self-assembly for stimuli-responsive drug release. The obtained thin films exhibited pH-responsive drug release in a controlled manner; pH 4.5 = 99.2% and pH 6.5 = 59.3% of doxorubicin (DOX) release was observed over 15 days. Supramolecular π-π stacking interactions between f-CNOs and DOX played a critical role in controlling drug release from thin films. Cell viability was studied with human osteoblast cells and augmented viability was perceived. Moreover, the thin films presented 891.4 ± 8.2 MPa of the tensile strength (σult), 43.2 ± 1.1 GPa of Young’s modulus (E), and 164.5 ± 1.7 Jg−1 of toughness (K). Quantitative scrutiny revealed that the well-ordered aligned nanofibers provide critical interphase, and this could be responsible for augmented tensile properties. Nonetheless, a pH-responsive and mechanically robust biocompatible thin-film system may show potential applications in the biomedical field.


2002 ◽  
Vol 739 ◽  
Author(s):  
H. McNally ◽  
S. W. Lee ◽  
D. Guo ◽  
M. Pingle ◽  
D. Bergstrom ◽  
...  

ABSTRACTBio-inspired assembly, through the use of bio-molecules such as DNA and proteins, will play a critical role in the advancement of novel sensing techniques and for the realization of heterogeneous integration of materials. For many of these applications, such as antibody-based biosensor and the study of controlled cell growth, DNA and protein patterning techniques are crucial. We will present an update of our work on protein patterning techniques using microelectronic fabrication, DNA hybridization and biotin-streptavidin pairing. To show its application in biological inspired self-assembly, this technique was used successfully in the self-assembly of 20 nm streptavidin conjugated gold particles. In addition, the integration of nano-and micro-scale heterogeneous materials is very important for novel material synthesis and electro-optic applications. We will present an update on our work to assemble silicon electronic devices using DNA/charged molecules and electric fields. Devices are fabricated, released, charged with molecules, and subsequently manipulated in electric fields. The techniques described can be used to integrate the hybrid devices such as nano- or micro-scale resistors, PN diodes, and MOSFETs on silicon or other substrates such as glass, plastic, etc.


Open Physics ◽  
2011 ◽  
Vol 9 (3) ◽  
Author(s):  
Arvydas Tamulis ◽  
Mantas Grigalavicius ◽  
Sarunas Krisciukaitis ◽  
Giedrius Medzevicius

AbstractDensity functional theory methods were used to investigate various self-assembled photoactive bioorganic systems of interest for artificial minimal cells. The cell systems studied are based on nucleotides or their compounds and consisted of up to 123 atoms (not including the associated water or methanol solvent shells) and are up to 2.5 nm in diameter. The electron correlation interactions responsible for the weak hydrogen and Van derWaals chemical bonds increase due to the addition of a polar solvent (water or methanol). The precursor fatty acid molecules of the system also play a critical role in the quantum mechanical interaction based self-assembly of the photosynthetic center and the functioning of the photosynthetic processes of the artificial minimal cells. The distances between the separated sensitizer, fatty acid precursor, and methanol molecules are comparable to Van derWaals and hydrogen bonding radii. As a result the associated electron correlation interactions compress the overall system, resulting in an even smaller gap between the highest occupied molecular orbital (HOMO), and lowest unoccupied molecular orbital (LUMO) electron energy levels and photoexcited electron tunnelling occurs from the sensitizer (either Ru(bpy)32+ or [Ru(bpy)2(4-Bu-4’-Me-2,2’-bpy)]2++ derivatives) to the precursor fatty acid molecules (notation used: Me = methyl; Bu = butyl; bpy = bipyridine). The shift of the absorption spectrum to the red for the artificial protocell photosynthetic centers might be considered as the measure of the complexity of these systems.


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