Soft Substrates Research Articles

High extracellular matrix stiffness promotes the metastasis of nasopharyngeal carcinoma through STAT3/FGF1 positive feedback regulation activated by JAK2

The stiffness of the extracellular matrix (EM) is known to be associated with tumor metastasis. This study aims to clarify the function and mechanisms of EM stiffness in nasopharyngeal carcinoma (NPC) and to provide a potential therapeutic target for patients with NPC. The NPC cell lines were cultured under varying stiffnesses. Plate cloning, Transwell assays and scratch tests were conducted to compare the phenotypes. Transcriptome sequencing and enrichment analysis were performed to explore the key molecules and the downstream signaling pathways, which were verified via in vitro and in vivo experiments. Our study showed that the NPC cells cultured on a stiff substrate (50 ​kPa) had greater colony formation, invasion and migration abilities than those cultured on a soft substrate. Transcriptome sequencing showed that a stiff environment induced high expression of fibroblast growth factor 1 (FGF1), which suggested a poor prognosis in various malignancies. The phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway played an important role in NPC metastasis activated by the FGF1 autocrine pathway in a stiff environment. The increased FGF1 expression was regulated by the transcription factor STAT3, and a positive feedback regulation between them was observed. The use of the JAK inhibitor Ruxolitinib and JAK2 interference inhibited the activation of STAT3. In conclusion, JAK2 activates STAT3/FGF1 positive feedback regulation and promotes NPC metastasis via the PI3K/Akt signaling pathway in a high-stiffness environment. Hence, FGF1 can be used as a potential therapeutic target for patients with NPC.

Formation mechanism of radial and circular cracks promoted by delamination in drying silica colloidal deposits.

Cracks with radial and circular patterns are appealing in nature and industry. Although morphologies and propagation conditions of cracks are extensively studied, the formation mechanism of crack pattern by the interaction of channel fracture and interfacial delamination remains elusive. Here, we present the transition of radial to coexisting radial and circular crack patterns when the thickness of colloidal deposits on both hard and soft substrates exceeds a critical value, through the colloidal volume fraction dependence. In addition, a thickness-dependent phase diagram from radial crack to coexistence of radial and circular cracks was constructed with respect to the radius and the volume fractions of silica colloidal deposits. A phase-field fracture model is developed to elucidate how the formation of radial cracks is facilitated by simultaneous delamination. The warping-induced radial tensile stress at the bottom surface of the striped deposit is proportional to the thickness. It leads to subsequent nucleation and growth of circular cracks in thick deposits. This work provides insight into the formation mechanism of complex crack patterns in drying colloidal deposits and revolutionizes the design space of crack-based micro-nano structures.

Oxygen-defective electrostrictors for soft electromechanics.

Electromechanical metal oxides, such as piezoceramics, are often incompatible with soft polymers due to their crystallinity requirements, leading to high processing temperatures. This study explores the potential of ceria-based thin films as electromechanical actuators for flexible electronics. Oxygen-deficient fluorites, like cerium oxide, are centrosymmetric nonpiezoelectric crystalline metal oxides that demonstrate giant electrostriction. These films, deposited at low temperatures, integrate seamlessly with various soft substrates like polyimide and PET. Ceria thin films exhibit remarkable electrostriction (M33 > 10-16 m2 V-2) and inverse pseudo-piezo coefficients (e33 > 500 pmV-1), enabling large displacements in soft electromechanical systems. Our study explores resonant and off-resonant configurations in the low-frequency regime (<1 kHz), demonstrating versatility for three-dimensional and transparent electronics. This work advances the understanding of oxygen-defective metal oxide electromechanical properties and paves the way for developing versatile and efficient electromechanical systems for applications in biomedical devices, optical devices, and beyond.

Temporal regulation of BMP2 growth factor signaling in response to mechanical loading is linked to cytoskeletal and focal adhesion remodeling

Biophysical cues have the ability to enhance cellular signaling response to Bone Morphogenetic Proteins, an essential growth factor during bone development and regeneration. Yet, therapeutic application of Bone Morphogenetic Protein 2 (BMP2) is restricted due to uncontrolled side effects. An understanding of the temporal characteristics of mechanically regulated signaling events and underlying mechanism is lacking. Using a 3D bioreactor system in combination with a soft macroporous biomaterial substrate, we mimic the in vivo environment that BMP2 is acting in. We show that the intensity and duration of BMP2 signaling increases with increasing loading frequency in synchrony with the number and size of focal adhesions. Long-term mechanical stimulation increases the expression of BMP receptor type 1B, specific integrin subtypes and integrin clustering. Together, this triggered a short-lived mechanical echo that enhanced BMP2 signaling even when BMP2 is administered directly after mechanical stimulation, but not when it is applied after a resting period of ≥30 min. Interfering with cytoskeletal remodeling hinders focal adhesion remodeling verifying its critical role in shifting cells into a state of high BMP2 responsiveness. The design of biomaterials that exploit this potential locally at the site of injury will help to overcome current limitations of clinical growth factor treatment.

A Computational Design Framework for Lubrication Interfaces With Active Micro-textures

Abstract The major goal of the present study is to develop a computational design framework for the active control of hydrodynamically lubricated interfaces. The framework ultimately delivers an electrode distribution on an elastomeric substrate such that a voltage-controlled texture may be induced on its surface. This enables the setup to attain a desired time-dependent macroscopic lubrication response. The computational framework is based on a numerically efficient two-stage design approach. In the first stage, a topology optimization framework is introduced for determining a microscopic texture and the uniform modulation of its amplitude. The objective is to attain the targeted fluid flux or frictional traction signals based on the homogenization-based macroscopic response of the texture. As a minor goal, a novel unit cell geometry optimization feature will be developed which will enable working in a design space that is as unrestricted as possible. The obtained designs are then transferred to the second stage where the electrode distribution on a soft substrate is determined along with the voltage variation that delivers the desired amplitude variation. The first stage operates in a two-dimensional setting based on the Reynolds equation whereas the second stage operates in a three-dimensional setting based on an electroelasticity formulation. The two stages are heuristically coupled by transferring the texture topology to the electrode distribution through a projection step. The viability of such an active lubrication interface design approach is demonstrated through numerous examples that methodically investigate the central features of the overall computational framework.

The interfacial behavior of a liquid crystal elastomer film bonded to an orthotropic substrate under light illumination

Bilayer soft actuators composed of a liquid crystal elastomer (LCE) film and a soft substrate have been widely used in soft robotics, bioengineering, and other fields. The existence of stress concentration at the interface edge easily leads to delamination damage of layered structures. Therefore, this article focuses on the distribution of interfacial stresses of the light-driven LCE film/orthotropic substrate system. The governing equations of the LCE film/substrate system are derived. The distributions of peeling and shear stresses on the interface are given and validated by using the finite element method (FEM). The effects of light illumination intensity, light attenuation distance and the director direction on the distribution of interfacial stresses are comprehensively analyzed. It is found that the signs of the shear stress and peeling stress depend on the director direction. This indicates that aligning the director in a certain direction may enhance the interface strength. The results may be useful for designing light-responsive LCE bilayer drivers.

Energy-efficient dynamic 3D metasurfaces via spatiotemporal jamming interleaved assemblies for tactile interfaces

Inspired by the natural shape-morphing abilities of biological organisms, we introduce a strategy for creating energy-efficient dynamic 3D metasurfaces through spatiotemporal jamming of interleaved assemblies. Our approach, diverging from traditional shape-morphing techniques reliant on continuous energy inputs, utilizes strategically jammed, paper-based interleaved assemblies. By rapidly altering their stiffness at various spatial points and temporal phases during the relaxation of the soft substrate through jamming, we enable the formation of refreshable, intricate 3D shapes with a desirable load-bearing capability. This process, which does not require ongoing energy consumption, ensures energy-efficient and lasting shape displays. Our theoretical model, linking buckling deformation to residual pre-strain, underpins the inverse design process for an array of interleaved assemblies, facilitating the creation of diverse 3D configurations. This metasurface holds notable potential for tactile displays, particularly for the visually impaired, heralding possibilities in visual impaired education, haptic feedback, and virtual/augmented reality applications.

Tailored environments for directed mesenchymal stromal cell proliferation and differentiation using decellularized extracellular matrices in conjunction with substrate modulus

Decellularised extracellular matrix (dECM) produced by mesenchymal stromal cells (MSCs) is a promising biomaterial for improving the ex vivo expansion of MSCs. The dECMs are often deposited on high modulus surfaces such as tissue culture plastic or glass, and subsequent differentiation assays often bias towards osteogenesis. We tested the hypothesis that dECM deposited on substrates of varying modulus will produce cell culture environments that are tailored to promote the proliferation and/or lineage-specific differentiation of MSCs. dECM was produced on type I collagen-functionalised polyacrylamide hydrogels with discrete moduli (∼4, 10, and 40 kPa) or in a linear gradient of modulus that spans the same range, and the substrates were used as culture surfaces for MSCs. Fluorescence spectroscopy and mass spectrometry characterization revealed structural compositional changes in the dECM as a function of substrate modulus. Softer substrates (4 kPa) with dECM supported the largest number of MSCs after 7 days (∼1.6-fold increase compared to glass). Additionally, osteogenic differentiation was greatest on high modulus substrates (40 kPa and glass) with dECM. Nuclear translocation of YAP1 was observed on all surfaces with a modulus of 10 kPa or greater and may be a driver for the increased osteogenesis on the high modulus surfaces. These data demonstrate that dECM technology can be integrated with environmental parameters such as substrate modulus to improve/tailor MSC proliferation and differentiation during ex vivo culture. These results have potential impact in the improved expansion of MSCs for tailored therapeutic applications and in the development of advanced tissue engineering scaffolds. Statement of significanceMesenchymal stromal cells (MSCs) are extensively used in tissue engineering and regenerative medicine due to their ability to proliferate, differentiate, and modulate the immune environment. Controlling MSC behavior is critical for advances in the field. Decellularised extracellular matrix (dECM) can maintain MSC properties in culture, increase their proliferation rate and capacity, and enhance their stimulated differentiation. Substrate stiffness is another key driver of cell function, and previous reports have primarily looked at dECM deposition and function on stiff substrates such as glass. Herein, we produce dECM on substrates of varying stiffness to create tailored environments that enhance desired MSC properties such as proliferation and differentiation. Additionally, we complete mechanistic studies including quantitative mass spec of the ECM to understand the biological function.

Printable, stretchable metal-vapor-desorption layers for high-fidelity patterning in soft, freeform electronics

High-fidelity patterning of thin metal films on arbitrary soft substrates promises integrated circuits and devices that can significantly augment the morphological functionalities of freeform electronics. However, existing patterning methods that decisively rely on prefabricated rigid masks are severely incompatible with myriad surfaces. Here, we report printable, stretchable metal-vapor-desorption layers (s-MVDLs) that can enable high-fidelity patterning of thin metal films on freeform polymeric surfaces. The printed rubbery matrix with highly mobile chains effectively repels various metal vapors from the surface and inhibits their condensation, thereby allowing selective metal deposition. The s-MVDLs are printed by direct ink writing techniques, enabling customizable and scalable thin metal patterns ranging from the micrometer to millimeter scale with high fidelity. Furthermore, the superior stretchability and mechanical robustness of the s-MVDLs allow highly compliant deformation along the substrates, enabling the construction of unconventional circuits and devices on multi-curvature, non-developable, and stretchable surfaces.

Characterization, enrichment, and computational modeling of cross-linked actin networks in trabecular meshwork cells.

Cross-linked actin networks (CLANs) are prevalent in the glaucomatous trabecular meshwork (TM), yet their role in ocular hypertension remains unclear. We used a human TM cell line that spontaneously forms fluorescently-labeled CLANs (GTM3L) to explore the origin of CLANs, developed techniques to increase CLAN incidence in GMT3L cells, and computationally studied the biomechanical properties of CLAN-containing cells. GTM3L cells were fluorescently sorted for viral copy number analysis. CLAN incidence was increased by (i) differential sorting of cells by adhesion, (ii) cell deswelling, and (iii) cell selection based on cell stiffness. GTM3L cells were also cultured on glass or soft hydrogel to determine substrate stiffness effects on CLAN incidence. Computational models were constructed to mimic and study the biomechanical properties of CLANs. All GTM3L cells had an average of 1 viral copy per cell. LifeAct-GFP expression level did not affect CLAN incidence rate, but CLAN rate was increased from ∼0.28% to ∼50% by a combination of adhesion selection, cell deswelling, and cell stiffness-based sorting. Further, GTM3L cells formed more CLANs on a stiff vs. a soft substrate. Computational modeling predicted that CLANs contribute to higher cell stiffness, including increased resistance of the nucleus to tensile stress when CLANs are physically linked to the nucleus. It is possible to greatly enhance CLAN incidence in GTM3L cells. CLANs are mechanosensitive structures that affect cell biomechanical properties. Further research is needed to determine the effect of CLANs on TM biomechanics and mechanobiology as well as the etiology of CLAN formation in the TM.

Materials, Structure, and Interface of Stretchable Interconnects for Wearable Bioelectronics.

Since wearable technologies for telemedicine have emerged to tackle global health concerns, the demand for well-attested wearable healthcare devices with high user comfort also arises. Skin-wearables for health monitoring require mechanical flexibility and stretchability for not only high compatibility with the skin's dynamic nature but also a robust collection of fine health signals from within. Stretchable electrical interconnects, which determine the device's overall integrity, are one of the fundamental units being understated in wearable bioelectronics. In this review, a broad class of materials and engineering methodologies recently researched and developed are presented, and their respective attributes, limitations, and opportunities in designing stretchable interconnects for wearable bioelectronics are offered. Specifically, the electrical and mechanical characteristics of various materials (metals, polymers, carbons, and their composites) are highlighted, along with their compatibility with diverse geometric configurations. Detailed insights into fabrication techniques that are compatible with soft substrates are also provided. Importantly, successful examples of establishing reliable interfacial connections between soft and rigid elements using novel interconnects are reviewed. Lastly, some perspectives and prospects of remaining research challenges and potential pathways for practical utilization of interconnects in wearables are laid out.

A multiscale modeling to determine in vitro mechanical responses of different cells at the cell-substrate interface under fluid perfusion.

Investigating the influence of different cellular mechanical and physical properties on cells in vitro is important for assessing cellular activities like differentiation, proliferation, and migration. Evaluating the mechanical response of the cells lodged on a scaffold due to variations in substrate roughness, substrate elasticity, fluid flow, and the shapes of the cells is the main goal of the study. In this comprehensive analysis, a combination of the fluid structure interaction method and the submodeled finite element technique was employed to anticipate the mechanical responses across various cells at the interface between cells and the substrate. Fluid inlet velocity, substrate roughness, and substrate material were varied in this analysis. Different cell shapes were considered along with various components such as cell membrane, cytoplasm, nucleus, and cytoskeletons. This analysis shows the effect of these individual parameters on the elastic strain and strain energy density of cells at the cell-substrate interface. The results highlight that substrate roughness has a more significant impact on the mechanical response of cells at the interface than substrate elasticity. However, effect of the substrate elasticity becomes crucial for extremely soft substrate materials. The results of this research can be applied to identify the optimal parameters for fluid flow and create a suitable condition for cell culture.

Structural and optical properties of Cu:CdS thin films on soft polymer substrate

Structural and optical properties of Cu:CdS thin films on soft polymer substrate

How to Keep Myofibroblasts under Control: Culture of Mouse Skin Fibroblasts on Soft Substrates

During the physiological healing of skin wounds, fibroblasts recruited from the uninjured adjacent dermis and deeper subcutaneous fascia layers are transiently activated into myofibroblasts to first secrete and then contract collagen-rich extracellular matrix into a mechanically resistant scar. Scar tissue restores skin integrity after damage but comes at the expense of poor esthetics and loss of tissue function. Stiff scar matrix also mechanically activates various precursor cells into myofibroblasts in a positive feedback loop. Persistent myofibroblast activation results in pathologic accumulation of fibrous collagen and hypertrophic scarring, called fibrosis. Consequently, the mechanisms of fibroblast-to-myofibroblast activation and persistence are studied to develop antifibrotic and prohealing treatments. Mechanistic understanding often starts in a plastic cell culture dish. This can be problematic because contact of fibroblasts with tissue culture plastic or glass surfaces invariably generates myofibroblast phenotypes in standard culture. We describe a straight-forward method to produce soft cell culture surfaces for fibroblast isolation and continued culture and highlight key advantages and limitations of the approach. Adding a layer of elastic silicone polymer tunable to the softness of normal skin and the stiffness of pathologic scars allows to control mechanical fibroblast activation while preserving the simplicity of conventional 2-dimensional cell culture.

Topological design of soft substrate acoustic metamaterial for mechanical tuning of sound propagation

The design of tunable acoustic waves is crucial in phononic crystals (PnCs), as acoustic waves exhibit continuous variation across diverse frequency ranges in practical applications. While there have been research efforts on tunable PnCs, existing design strategies predominantly rely on predetermined topology and scatterer shapes based on empirical experience. This reliance poses challenges in ensuring customized and reversible tuning of the bandgap. In this work, we present a customized tunable PnC design model and solution strategy based on soft substrates, which enables reversible tuning of a specific frequency/order bandgap. The designed structure consists of a soft substrate and crystalline columns dispersed in the soft substrate and air. The relative positions of the scatterers in the air are changed by stretching the substrate, thereby realizing the modulation of sound propagation. Since soft materials have both material nonlinearities and complex geometrical variations that are difficult to obtain design sensitivity information, the material-field series expansion topology optimization approach is employed to achieve custom tunable design of the bandgap. The paper presents simulation-based analyses and experimental verification of the customized bandgap opening and closing. The results demonstrate a close alignment between theoretical predictions of propagation curves and experimental findings. This concurrence serves as evidence that the soft-substrate PnC, derived through topology optimization, effectively facilitates the adjustment of bandgaps of arbitrary orders and enables switching between various acoustic functions.

FlexScale: Modeling and Characterization of Flexible Scaled Sheets

We present a computational approach for modeling the mechanical behavior of flexible scaled sheet materials---3D-printed hard scales embedded in a soft substrate. Balancing strength and flexibility, these structured materials find applications in protective gear, soft robotics, and 3D-printed fashion. To unlock their full potential, however, we must unravel the complex relation between scale pattern and mechanical properties. To address this problem, we propose a contact-aware homogenization approach that distills native-level simulation data into a novel macromechanical model. This macro-model combines piecewise-quadratic uniaxial fits with polar interpolation using circular harmonics, allowing for efficient simulation of large-scale patterns. We apply our approach to explore the space of isohedral scale patterns, revealing a diverse range of anisotropic and nonlinear material behaviors. Through an extensive set of experiments, we show that our models reproduce various scale-level effects while offering good qualitative agreement with physical prototypes on the macro-level.

International Biological Flora: Trapa natans†

Abstract This account presents information on all aspects of the biology of Trapa natans L. (water caltrop and water chestnut) that are relevant to understanding its ecological characteristics and behaviour. The main topics are presented within the standard framework of the International Biological Flora: distribution, habitat, communities, responses to biotic factors, responses to environment, structure and physiology, phenology, floral and seed characters, herbivores and disease, history, conservation and global heterogeneity. The water caltrop is an annual herbaceous hydrophyte rooted in the sediment of water bodies, forming flexuous underwater stems that create a buoyant, light‐capturing leaf rosette at the water surface. The submerged stem nodes additionally bear linear leaves. These are replaced by photosynthetically active, pinnately branched structures and unbranched adventitious roots early on, which complement previously established roots on the hypocotyl, altogether facilitating anchorage, nutrient and water absorption, aeration and capture of subsurface irradiance. Solitary flowers pollinated primarily through autogamy and incidentally through entomophily give rise to a fully developed edible single‐seeded drupe with two to four barbed horns. Fruits are dispersed with the help of hydrochory, epizoochory and anthropochory. Throughout its lowland, global temperate, subtropical and tropical distribution in Eurasia and Africa, the thermophilic macrophyte is found in shallow, sun‐exposed, nutrient‐rich freshwater bodies with low‐velocity flows and steady water levels. These offer slightly acidic to mildly basic conditions. The accompanying soft substrate is usually characterized by a high organic matter content. Regularly co‐occurring with other macrophytes, some of which are also of conservation concern, such as those in rare stands of the association Trapetum natantis in Europe, the water caltrop has at times been outcompeted, though it may form monodominant stands, due to several competitive features. Formerly widespread in Europe, T. natans is today recognized as a rare, strictly protected macrophyte. It has been introduced to Australia and North America; on the latter continent, its naturalization, spread and aggressive overgrowth have led to extensive control efforts. Having been used as a crop since Neolithic times, it is still exploited in Asia for means of food production, phytoremediation, ornamental purposes, medication and alternative uses.

Flow‐induced interfacial deformation structures (FIDS): Implications for the interpretation of palaeocurrents, flow dynamics and substrate rheology

ABSTRACTSole structures on the base of turbidites, and other bed types, are typically classified into scour marks and tool marks, such as flutes, grooves, skim marks and prod marks. Yet, there are a range of other common sole marks that are unrelated to scouring or tools, and whose origin is poorly understood. Prominent among these sole structures are longitudinal ridges and furrows, and ‘dinosaur leather’ structures associated with mud ripples. Herein, these features are described and it is argued that they are the product of deformation of the substrate during a sediment gravity flow event. In these flow‐induced interfacial deformation structures (FIDS), a soft cohesive substrate undergoes deformation in response to a buoyant force induced by the denser basal component of an overriding flow, and the flow interacts with this buoyant deformation through shear to remould the substrate. Variations in the relative strength of these buoyant and shear‐induced forces explain the wide range of FIDS that can form. This FIDS model reinterprets the formation of longitudinal ridges and furrows, which have previously been classified as scour marks, and explains their distinctive spatial patterns. Furthermore, the new model builds on the seminal work of Dżułyński and colleagues in the 1960s and 1970s, who identified that these structures contain key palaeocurrent information, and it is argued that such information is largely under‐utilized. Importantly, alongside their utility as palaeocurrent indicators, FIDS provide insights into the rheology of the substrate at the time of their formation, and thus the nature of basal flow conditions in the formative flows.

Integrating the Stimuli‐Responsiveness of Microparticles via Matrix Embedding for Smart Soft Materials with Customized Switchable Properties

AbstractSmart soft materials are the focus of extensive research efforts due to their potential applications in various fields. Inspired by nature, embedding smart micro‐inclusions in a soft substrate provides a feasible strategy to integrate the smartness of individual microparticles for creating smart materials at the macroscale, broadening the capabilities and applications of smart soft materials. This strategy decouples the design of intelligence and substrate materials, leading to a broader design space for both the smartness and the mechanical properties of the composites. In this Perspective, recent advances in creating smart soft materials using smart microparticles are summarized. The methods developed to construct composites of microparticles in a soft matrix are first introduced, followed by detailed discussions on the material compositions, stimuli and responsiveness, and properties of individual microparticles and the composite systems. Various applications based on advanced functionalities and capabilities that are enabled by those smart soft materials are highlighted. This study also points out research directions to further advance unconventional smart soft materials following this bioinspired approach.

Multifunctional Nanomesh Enables Cellular-Resolution, Elastic Neuroelectronics.

Silicone-based devices have the potential to achieve an ideal interface with nervous tissue but suffer from scalability, primarily due to the mechanical mismatch between established electronic materials and soft elastomer substrates. This study presents a novel approach using conventional electrode materials through multifunctional nanomesh to achieve reliable elastic microelectrodes directly on polydimethylsiloxane (PDMS) silicone with an unprecedented cellular resolution. This engineered nanomesh features an in-plane nanoscale mesh pattern, physically embodied by a stack of three thin-film materials by design, namely Parylene-C for mechanical buffering, gold (Au) for electrical conduction, and Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) for improved electrochemical interfacing. Nanomesh elastic neuroelectronics are validated using single-unit recording from the small and curvilinear epidural surface of mouse dorsal root ganglia (DRG) with device self-conformed and superior recording quality compared to plastic control devices requiring manual pressing is demonstrated. Electrode scaling studies from in vivo epidural recording further revealed the need for cellular resolution for high-fidelity recording of single-unit activities and compound action potentials. In addition to creating a minimally invasive device to effectively interface with DRG sensory afferents at a single-cell resolution, this study establishes nanomeshing as a practical pathway to leverage traditional electrode materials for a new class of elastic neuroelectronics.