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1. Cell mediated remodeling of stiffness matched collagen and fibrin scaffolds

   https://doi.org/10.1038/s41598-022-14953-w  

   Jagiełło, Alicja; Castillo, Ulysses; Botvinick, Elliot (December 2022, Scientific Reports)

   Abstract Cells are known to continuously remodel their local extracellular matrix (ECM) and in a reciprocal way, they can also respond to mechanical and biochemical properties of their fibrous environment. In this study, we measured how stiffness around dermal fibroblasts (DFs) and human fibrosarcoma HT1080 cells differs with concentration of rat tail type 1 collagen (T1C) and type of ECM. Peri-cellular stiffness was probed in four directions using multi-axes optical tweezers active microrheology (AMR). First, we found that neither cell type significantly altered local stiffness landscape at different concentrations of T1C. Next, rat tail T1C, bovine skin T1C and fibrin cell-free hydrogels were polymerized at concentrations formulated to match median stiffness value. Each of these hydrogels exhibited distinct fiber architecture. Stiffness landscape and fibronectin secretion, but not nuclear/cytoplasmic YAP ratio differed with ECM type. Further, cell response to Y27632 or BB94 treatments, inhibiting cell contractility and activity of matrix metalloproteinases, respectively, was also dependent on ECM type. Given differential effect of tested ECMs on peri-cellular stiffness landscape, treatment effect and cell properties, this study underscores the need for peri-cellular and not bulk stiffness measurements in studies on cellular mechanotransduction. 

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2. Fibrin-Polycaprolactone Scaffolds for the Differentiation of Human Neural Progenitor Cells into Dopaminergic Neurons

   https://doi.org/10.1021/acsomega.4c03952  

   Ramirez, Salma_P; Hernandez, Ivana; Dorado, Zayra_N; Loyola, Carla_D; Roberson, David_A; Joddar, Binata (August 2024, ACS Omega)
3. Fabrication and Characterization of Quad-Component Bioinspired Hydrogels to Model Elevated Fibrin Levels in Central Nervous Tissue Scaffolds

   https://doi.org/10.3390/gels10030203  

   Diaz-Lasprilla, Ana M; McKee, Meagan; Jimenez-Vergara, Andrea C; Ravi, Swathisri; Bellamy, Devon; Ortega, Wendy; Crosby, Cody O; Steele, Jennifer; Plascencia-Villa, Germán; Perry, George; et al (March 2024, Gels)

   Kakehashi, Rie; Yamashita, Yuji (Ed.)

   Multicomponent interpenetrating polymer network (mIPN) hydrogels are promising tissue-engineering scaffolds that could closely resemble key characteristics of native tissues. The mechanical and biochemical properties of mIPNs can be finely controlled to mimic key features of target cellular microenvironments, regulating cell-matrix interactions. In this work, we fabricated hydrogels made of collagen type I (Col I), fibrin, hyaluronic acid (HA), and poly (ethylene glycol) diacrylate (PEGDA) using a network-by-network fabrication approach. With these mIPNs, we aimed to develop a biomaterial platform that supports the in vitro culture of human astrocytes and potentially serves to assess the effects of the abnormal deposition of fibrin in cortex tissue and simulate key aspects in the progression of neuroinflammation typically found in human pathologies such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and tissue trauma. Our resulting hydrogels closely resembled the complex modulus of AD human brain cortex tissue (~7.35 kPa), promoting cell spreading while allowing for the modulation of fibrin and hyaluronic acid levels. The individual networks and their microarchitecture were evaluated using confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). Human astrocytes were encapsulated in mIPNs, and negligible cytotoxicity was observed 24 h after the cell encapsulation. 

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4. Deconstructing fibrin(ogen) structure

   https://doi.org/10.1016/j.jtha.2024.10.024  

   Risman, Rebecca A; Sen, Mehmet; Tutwiler, Valerie; Hudson, Nathan E (November 2024, Journal of Thrombosis and Haemostasis)
5. Actively Driven Fluctuations in a Fibrin Network

   https://doi.org/10.3389/fphy.2020.568736  

   Hu, Qingda; Morris, Tessa Altair; Grosberg, Anna; Levine, Alex J.; Botvinick, Elliot L. (February 2021, Frontiers in Physics)

   null (Ed.)

   Understanding force propagation through the fibrous extracellular matrix can elucidate how cells interact mechanically with their surrounding tissue. Presumably, due to elastic nonlinearities of the constituent filaments and their random connection topology, force propagation in fiber networks is quite complex, and the basic problem of force propagation in structurally heterogeneous networks remains unsolved. We report on a new technique to detect displacements through such networks in response to a localized force, using a fibrin hydrogel as an example. By studying the displacements of fibers surrounding a two-micron bead that is driven sinusoidally by optical tweezers, we develop maps of displacements in the network. Fiber movement is measured by fluorescence intensity fluctuations recorded by a laser scanning confocal microscope. We find that the Fourier magnitude of these intensity fluctuations at the drive frequency identifies fibers that are mechanically coupled to the driven bead. By examining the phase relation between the drive and the displacements, we show that the fiber displacements are, indeed, due to elastic couplings within the network. Both the Fourier magnitude and phase depend on the direction of the drive force, such that displacements typically propagate farther, but not exclusively, along the drive direction. This technique may be used to characterize the local mechanical response in 3-D tissue cultures, and to address fundamental questions about force propagation within fiber networks. 

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