Featured
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An intelligent DNA nanodevice for precision thrombolysis
An intelligent DNA nanodevice, composed of DNA origami nanosheets and a thrombin-responsive DNA fastener, accurately delivers the appropriate dose of tissue plasminogen activator following activation by distinct thrombosis events.
- Jue Yin
- , Siyu Wang
- & Lianhui Wang
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News & Views |
A thicker skin for better immune evasion
Cancer cells adjust the composition of their glycocalyx to increase its thickness and create a physical barrier that shields them from immune recognition and engagement.
- Edward N. Schmidt
- & Matthew S. Macauley
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Article
| Open AccessDrinkable in situ-forming tough hydrogels for gastrointestinal therapeutics
Sequential drinks of crosslinker and polymer solutions form a tough hydrogel in the stomach, enabling delivery of drugs and biologics in this harsh chemical environment.
- Gary W. Liu
- , Matthew J. Pickett
- & Giovanni Traverso
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Article |
Immunoengineering can overcome the glycocalyx armour of cancer cells
A nanoscale polymer layer formed by mucins at the surface of tumour cells protects them against immune cell attack. This shield can be circumvented through immune cell engineering, using chimeric antigen receptors to stimulate natural killer and T cells or by tethering glycocalyx-editing enzymes to immune cells.
- Sangwoo Park
- , Marshall J. Colville
- & Matthew J. Paszek
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Editorial |
Life-saving vaccines awarded
The fundamental discoveries that enabled the development of effective mRNA vaccines against COVID-19 were awarded with this year’s Nobel Prize in Medicine.
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News & Views |
Taming CAR T cell therapy toxicity
Post-infusion poly(ethylene glycol) surface modification of chimeric antigen receptor (CAR)-engineered T cells and a subcutaneous chemokine-adsorbing hydrogel address cytokine release syndrome and the neurotoxicity side effects of CAR T cell therapy against tumours.
- Chuang Liu
- & Khalid Shah
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News & Views |
Genetically encoded protein crystals by hierarchical design
Three protein interaction surfaces are computationally designed into one protein subunit to enable their accurate assembly into three-dimensional crystals with user-specified lattice architectures.
- Eduardo Anaya-Plaza
- & Mauri A. Kostiainen
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Article |
Cell volume expansion and local contractility drive collective invasion of the basement membrane in breast cancer
Forces resulting from global cell volume expansion and local cell contractions distort the basement membrane of an in vitro three-dimensional model of breast cancer, to promote collective cell invasion that precedes metastasis.
- Julie Chang
- , Aashrith Saraswathibhatla
- & Ovijit Chaudhuri
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News & Views |
Lymphatics drain nanoparticles from tumours
Lymphatic vessels within and near to tumours facilitate nanoparticle transport out of tumours, with ramifications in the design and implementation of next-generation clinical cancer nanomedicines.
- Meghan J. O’Melia
- & Susan N. Thomas
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News & Views |
Seriously non-thermal thermodynamics
Non-equilibrium thermodynamics describes activity-stabilized mixed states in complex active-matter systems.
- Tian Huang
- , Qi Pan
- & Steve Granick
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Article |
Pro-regenerative biomaterials recruit immunoregulatory dendritic cells after traumatic injury
Pro-regenerative biomaterials for the treatment of muscle injury induce the proliferation of a dendritic cell population associated with cross-presentation and self-tolerance, promoting a pro-regenerative immune environment to aid muscle wound healing.
- Ravi Lokwani
- , Aditya Josyula
- & Kaitlyn Sadtler
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Article
| Open AccessMagneto-acoustic protein nanostructures for non-invasive imaging of tissue mechanics in vivo
Magneto-gas vesicles, protein nanostructures with enhanced ultrasound signal and sensitivity, enable the non-invasive, long-term and quantitative monitoring of the mechanics of three-dimensional tissues and animals.
- Whee-Soo Kim
- , Sungjin Min
- & Jinwoo Cheon
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Accurate computational design of three-dimensional protein crystals
The process of protein crystallization is poorly understood and difficult to program through the primary sequence. Here the authors develop a computational approach to designing three-dimensional protein crystals with prespecified lattice architectures with high accuracy.
- Zhe Li
- , Shunzhi Wang
- & David Baker
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Article
| Open AccessThe laminin–keratin link shields the nucleus from mechanical deformation and signalling
Laminin, an important component of the extracellular matrix supporting the epithelium, hinders the typical mechanoresponse of epithelial cells to an increase in substrate stiffness, by protecting the cell nucleus from mechanical deformation.
- Zanetta Kechagia
- , Pablo Sáez
- & Pere Roca-Cusachs
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Article |
In situ PEGylation of CAR T cells alleviates cytokine release syndrome and neurotoxicity
Polyethylene glycol conjugation to chimeric antigen receptor T (CAR T) cells creates a physical block between CAR T cell interactions and other immune and tumour cells, controlling tumour lysis and immune response stimulation to mitigate cytokine release syndrome.
- Ningqiang Gong
- , Xuexiang Han
- & Michael J. Mitchell
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Article |
The exit of nanoparticles from solid tumours
Nanoparticle retention inside tumours has been associated with lymphatic vessel collapse. It is now shown that nanoparticles exit from solid tumours through lymphatic vessels in or surrounding the tumour by a nanoparticle-size-dependent mechanism.
- Luan N. M. Nguyen
- , Zachary P. Lin
- & Warren C. W. Chan
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Article |
Fibre-infused gel scaffolds guide cardiomyocyte alignment in 3D-printed ventricles
A gelatin–alginate hydrogel ink incorporating short gelatin fibres guides the self-organization of human cardiomyocytes into contractile tissues that can be 3D-printed into structures mimicking human organs.
- Suji Choi
- , Keel Yong Lee
- & Kevin Kit Parker
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Article |
Compressive forces stabilize microtubules in living cells
Microtubules respond to mechanical compression by deforming, becoming more stable, which results in CLASP2 recruitment to the distorted shaft—a process crucial for cell migration through confined spaces.
- Yuhui Li
- , Ondřej Kučera
- & Manuel Théry
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Article |
Photo-expansion microscopy enables super-resolution imaging of cells embedded in 3D hydrogels
Photopolymerizable hydrogels enable optical clearance and high homogeneous expansion for high-resolution optical imaging of cells embedded within degradable hydrogels.
- Kemal Arda Günay
- , Tze-Ling Chang
- & Kristi S. Anseth
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News & Views |
Unjamming tumour cell invasion through cGAS–STING
Locally confined epithelial malignancies undergo a phase transition from a solid-like to liquid-like state, a process called unjamming, where associated chronic intracellular strain causes nuclear envelope rupture, leading to the emergence of pro-metastatic traits due to cGAS–STING pathway activation.
- Matthew Deyell
- & Samuel F. Bakhoum
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News & Views |
Exosome-disrupting peptides for cancer immunotherapy
A curvature-sensing peptide is used to disrupt exosomes for enhanced cancer immunotherapy.
- Ningqiang Gong
- , Alex G. Hamilton
- & Michael J. Mitchell
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Article |
Curvature-sensing peptide inhibits tumour-derived exosomes for enhanced cancer immunotherapy
A curvature-sensing antiviral peptide is repurposed to disrupt tumour-derived exosomes and used in combination with immune checkpoint blockade cancer therapy.
- Sol Shin
- , Hyewon Ko
- & Jae Hyung Park
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Review Article |
Hydrogels for RNA delivery
RNA-based therapeutics hold promise for the treatment of several diseases. This Review provides an overview of hydrogels for RNA delivery, discussing how the chemical nature and physical properties of hydrogels can be explored for tailored RNA loading and release, and highlighting the use of these materials in biomedical applications.
- Ruibo Zhong
- , Sepehr Talebian
- & Jinjun Shi
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News & Views |
A synthetic tumour microenvironment
A bioengineered model incorporating a synthetic extracellular matrix recapitulates the lymphoid tumour microenvironment, making it a valuable tool for drug testing and designing personalized therapies.
- Akhilesh K. Gaharwar
- & Irtisha Singh
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Article |
Combinatorial treatment rescues tumour-microenvironment-mediated attenuation of MALT1 inhibitors in B-cell lymphomas
A hydrogel-based modular lymphoma organoid identifies how lymphoid microenvironment cues dampen the effect of MALT1 inhibitors and informs effective combination therapies to rescue the treatment response
- Shivem B. Shah
- , Christopher R. Carlson
- & Ankur Singh
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News & Views |
Immunostimulatory nanoparticles go viral
A polymeric nanoparticle adjuvant containing a Toll-like receptor 7 agonist elicits broad protection against viral challenges.
- Jorge Huete-Carrasco
- & Ed C. Lavelle
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News & Views |
Inhalable mRNA nanoparticles
A large-scale screening identifies an inhalable polymer nanoparticle formulation that safely and effectively delivers therapeutic mRNA molecules to the lungs of several animal species.
- Ronnie H. Fang
- & Liangfang Zhang
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News & Views |
Exploiting endothelial transcytosis to reach into the brain
Targeting P-selectin enables safer and more effective nanomedicine delivery through caveolin-1-mediated endothelial transcytosis in preclinical medulloblastoma tumour models.
- Lin Wang
- & Stefan Wilhelm
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Article
| Open AccessP-selectin-targeted nanocarriers induce active crossing of the blood–brain barrier via caveolin-1-dependent transcytosis
Targeting of tumour vasculature endothelial P-selectin promotes caveolin-1-mediated transcytosis for enhanced blood–brain barrier crossing of therapeutic nanoparticles against medulloblastoma.
- Daniel E. Tylawsky
- , Hiroto Kiguchi
- & Daniel A. Heller
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An inhaled bioadhesive hydrogel to shield non-human primates from SARS-CoV-2 infection
A bioadhesive hydrogel delivered via inhalation efficiently coats the airway and restricts SARS-CoV-2 virus variant penetration in mice and non-human primates
- Xuan Mei
- , Junlang Li
- & Ke Cheng
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Editorial |
Simple connections take the prize
Click chemistry and bioorthogonal chemistry have finally been recognized with the Nobel Prize in Chemistry.
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News & Views |
A bioadhesive robot to activate muscles
Soft actuators composed of a tough bioadhesive/elastomer shell encapsulating a stimuli-responsive metallic spring provide in situ mechanical stimulation of skeletal muscles to promote muscle tissue rehabilitation and prevent atrophy.
- Xuanhe Zhao
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Article
| Open AccessA TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2
A nanoparticle-based adjuvant incorporating a Toll-like receptor 7 agonist elicits cross-reactive antibodies for both dominant and subdominant epitopes and enhances immune responses against multiple variants of influenza and SARS-CoV-2.
- Qian Yin
- , Wei Luo
- & Mark M. Davis
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Article
| Open AccessPolarity and chirality control of an active fluid by passive nematic defects
Defects of a passive nematic liquid crystal made from actin filaments pattern the collective behaviour of active microtubules, creating macroscopic polar patterns and chiral loops.
- Alfredo Sciortino
- , Lukas J. Neumann
- & Andreas R. Bausch
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Article
| Open AccessTissue fluidification promotes a cGAS–STING cytosolic DNA response in invasive breast cancer
Tissue fluidification in invasive breast carcinoma is accompanied by mechanical stresses that compromise nuclear integrity and liberate DNA, resulting in the activation of a pro-inflammatory response that shape tumour evolution and progression.
- Emanuela Frittoli
- , Andrea Palamidessi
- & Giorgio Scita
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Article
| Open AccessMechanics of the cellular microenvironment as probed by cells in vivo during zebrafish presomitic mesoderm differentiation
During mesodermal differentiation of living zebrafish embryos, individual cells probe the stiffness associated with the foam-like architecture of the tissue as a part of their mechanosensing responses.
- Alessandro Mongera
- , Marie Pochitaloff
- & Otger Campàs
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Matrix viscoelasticity controls spatiotemporal tissue organization
Viscoelasticity is a universal mechanical feature of the extracellular matrix. Here the authors show that the extracellular matrix viscoelasticity guides tissue growth and symmetry breaking, a fundamental process in morphogenesis and oncogenesis.
- Alberto Elosegui-Artola
- , Anupam Gupta
- & David J. Mooney
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Review Article |
Hierarchically structured bioinspired nanocomposites
This Review discusses recent progress in bioinspired nanocomposite design, emphasizing the role of hierarchical structuring at distinct length scales to create multifunctional, lightweight and robust structural materials for diverse technological applications.
- Dhriti Nepal
- , Saewon Kang
- & Hendrik Heinz
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Species-agnostic polymeric formulations for inhalable messenger RNA delivery to the lung
Screening of hundreds of nanoparticle polymers identifies an effective and low-toxicity formulation for the functional delivery of RNA to the lungs of distinct animal species.
- Laura Rotolo
- , Daryll Vanover
- & Philip J. Santangelo
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News & Views |
Steering from the rear
In the absence of biochemical gradients, cancer cell migration over fibrillar isotropic collagen can occur by a mechanical self-steering process involving asymmetric matrix deformation from the rear.
- Katarina Wolf
- & Peter Friedl
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Letter |
Weak catch bonds make strong networks
Reconstituted cytoskeleton networks linked with catch bonds display increased mechanical strength and crack resistance than those containing slip bonds, and simultaneously being more deformable, which allows for better adaptability to new mechanical environments.
- Yuval Mulla
- , Mario J. Avellaneda
- & Gijsje H. Koenderink
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News & Views |
In search of a softer environment
By maximizing cell–substrate force transmission, cancer cells can migrate towards either stiffer or softer substrate regions.
- Amy E. M. Beedle
- & Pere Roca-Cusachs
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Comment |
Ascendancy of semi-synthetic biomaterials from design towards democratization
Semi-synthetic goldilocks material design integrates the tunable characteristics of synthetic materials and the refined complexity of natural components, enabling for the progress of biomaterials across length scales. Accelerated translational success may thus be possible for more personalized and accessible products.
- Alessondra T. Speidel
- , Christopher L. Grigsby
- & Molly M. Stevens
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Article
| Open AccessCell clusters softening triggers collective cell migration in vivo
Collective cell migration in embryonic tissues is triggered by cell softening due to a microtubule deacetylation pathway involving the mechanosensitive ion channel Piezo1.
- Cristian L. Marchant
- , Abdul N. Malmi-Kakkada
- & Elias H. Barriga
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Transient nuclear deformation primes epigenetic state and promotes cell reprogramming
Mechanical confinement of fibroblasts into micrometre-sized channels deforms the cell nucleus, leading to temporary nuclear lamina destablization and disassembly, loss of lamina-associated domains in chromatin and a decrease in histone and DNA methylation. These mechanically induced alterations in chromatin boost the conversion of fibroblasts into neurons and pluripotent stem cells and thus can be explored for cell engineering applications.
- Yang Song
- , Jennifer Soto
- & Song Li
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Mechanical checkpoint regulates monocyte differentiation in fibrotic niches
Myelofibrosis causes a pathological remodelling of the bone marrow, which becomes stiffer and more elastic, thus promoting the proliferation of proinflammatory monocytes and their differentiation into dendritic cells.
- Kyle H. Vining
- , Anna E. Marneth
- & David J. Mooney
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Directed cell migration towards softer environments
Directed cell movement known as durotaxis, typically associated with cellular migration in response to a substrate gradient of increasing stiffness, is now shown to also occur in the opposite direction, following a gradient of decreasing stiffness.
- Aleksi Isomursu
- , Keun-Young Park
- & David J. Odde
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News & Views |
Multi-channel control of fruit fly behaviour
Fruit flies injected with magnetic nanoparticles and genetically modified to sensitize neural circuits to the rate of change in temperature have enabled subsecond behavioural responses to magnetic stimuli and multi-channel magnetic control.
- Michael G. Christiansen
- & Simone Schuerle
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