Substrate stiffness in nerve cells

Si, Weijin; Gong, Jihong; Yang, Xiaofei

doi:10.26599/bsa.2023.9050002

Cited by 7 publications

(4 citation statements)

References 77 publications

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“…Despite the growing importance of PEGylated fibrin hydrogels, little is known about their mechanical properties, and even less about their evolution with time in realistic experimental conditions. Indeed, the mechanical properties of the matrix can affect axon stability and development, which can result in different neuronal networks depending on the final stiffness of the material [ 22 , 48 , 49 ]. The relative composition of thrombin and fibrinogen in the fibrin hydrogel significantly influences its bulk properties [ 32 ].…”

Section: Resultsmentioning

confidence: 99%

Rheological Characterization of Three-Dimensional Neuronal Cultures Embedded in PEGylated Fibrin Hydrogels

López-León

Soriano

Planet

2023

Gels

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Three-dimensional (3D) neuronal cultures are valuable models for studying brain complexity in vitro, and the choice of the bulk material in which the neurons grow is a crucial factor in establishing successful cultures. Indeed, neuronal development and network functionality are influenced by the mechanical properties of the selected material; in turn, these properties may change due to neuron–matrix interactions that alter the microstructure of the material. To advance our understanding of the interplay between neurons and their environment, here we utilized a PEGylated fibrin hydrogel as a scaffold for mouse primary neuronal cultures and carried out a rheological characterization of the scaffold over a three-week period, both with and without cells. We observed that the hydrogels exhibited an elastic response that could be described in terms of the Young’s modulus E. The hydrogels without neurons procured a stable E≃420 Pa, while the neuron-laden hydrogels showed a higher E≃590 Pa during the early stages of development that decreased to E≃340 Pa at maturer stages. Our results suggest that neurons and their processes dynamically modify the hydrogel structure during development, potentially compromising both the stability of the material and the functional traits of the developing neuronal network.

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Section: Resultsmentioning

confidence: 99%

Rheological Characterization of Three-Dimensional Neuronal Cultures Embedded in PEGylated Fibrin Hydrogels

López-León

Soriano

Planet

2023

Gels

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“…We note that thrombin concentration not only regulates the stiffness and architecture of the fibrin structure, but also the stability of the gel when used for culturing cells. Tissue stiffness determines the length of neuronal axons and their degree of spreading [41][42][43]. Therefore, the mechanical characterization of hydrogels is in general important to understand the behavior and emerging functional organization of the neuronal network growing within them.…”

Section: Discussion: Hydrogel Stability and Network Formationmentioning

confidence: 99%

Preparation and Mechano-Functional Characterization of PEGylated Fibrin Hydrogels: Impact of Thrombin Concentration

López-León,

Planet,

Soriano

2024

Gels

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Three-dimensional (3D) neuronal cultures grown in hydrogels are promising platforms to design brain-like neuronal networks in vitro. However, the optimal properties of such cultures must be tuned to ensure a hydrogel matrix sufficiently porous to promote healthy development but also sufficiently rigid for structural support. Such an optimization is difficult since it implies the exploration of different hydrogel compositions and, at the same time, a functional analysis to validate neuronal culture viability. To advance in this quest, here we present a combination of a rheological protocol and a network-based functional analysis to investigate PEGylated fibrin hydrogel networks with gradually higher stiffness, achieved by increasing the concentration of thrombin. We observed that moderate thrombin concentrations of 10% and 25% in volume shaped healthy networks, although the functional traits depended on the hydrogel stiffness, which was much higher for the latter concentration. Thrombin concentrations of 65% or higher led to networks that did not survive. Our results illustrate the difficulties and limitations in preparing 3D neuronal networks, and stress the importance of combining a mechano-structural characterization of a biomaterial with a functional one.

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“…This altered mechanical signaling from the extracellular space can be sensed via integrin receptors on the membrane and Hippo pathway and consequently triggers cytoskeleton remodeling as a response (Cai et al, 2021 ). Increased stiffness of brain tissue may cause age-related alterations such as loss of function of progenitor cells over time (Segel et al, 2019 ) or modulation of neuronal morphology (Si et al, 2023 ). The relationship between NDR kinases and ECM is tightly conserved across species.…”

Section: Altered Intracellular Communicationmentioning

confidence: 99%

The NDR family of kinases: essential regulators of aging

Jonischkies,

del Angel,

Demiray

et al. 2024

Front. Mol. Neurosci.

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Aging is defined as a progressive decline of cognitive and physiological functions over lifetime. Since the definition of the nine hallmarks of aging in 2013 by López-Otin, numerous studies have attempted to identify the main regulators and contributors in the aging process. One interesting group of proteins whose participation has been implicated in several aging hallmarks are the nuclear DBF2-related (NDR) family of serine-threonine AGC kinases. They are one of the core components of the Hippo signaling pathway and include NDR1, NDR2, LATS1 and LATS2 in mammals, along with its highly conserved metazoan orthologs; Trc in Drosophila melanogaster, SAX-1 in Caenorhabditis elegans, CBK1, DBF20 in Saccharomyces cerevisiae and orb6 in Saccharomyces pombe. These kinases have been independently linked to the regulation of widely diverse cellular processes disrupted during aging such as the cell cycle progression, transcription, intercellular communication, nutrient homeostasis, autophagy, apoptosis, and stem cell differentiation. However, a comprehensive overview of the state-of-the-art knowledge regarding the post-translational modifications of and by NDR kinases in aging has not been conducted. In this review, we summarize the current understanding of the NDR family of kinases, focusing on their relevance to various aging hallmarks, and emphasize the growing body of evidence that suggests NDR kinases are essential regulators of aging across species.

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Substrate stiffness in nerve cells

Cited by 7 publications

References 77 publications

Rheological Characterization of Three-Dimensional Neuronal Cultures Embedded in PEGylated Fibrin Hydrogels

Rheological Characterization of Three-Dimensional Neuronal Cultures Embedded in PEGylated Fibrin Hydrogels

Preparation and Mechano-Functional Characterization of PEGylated Fibrin Hydrogels: Impact of Thrombin Concentration

The NDR family of kinases: essential regulators of aging

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