Abstract:
UNLABELLED:Epithelial cellular heterogeneity has been observed in pathological tissues with abnormal matrix stiffness and cells cultured on rigid substrates. However, it remains unclear how matrix stiffness influences cellular heterogeneity formation in multi-cellular population. Here, we demonstrated that cellular heterogeneity regulated by substrate stiffness is evident starting from the initial single-cell stage (indicated by cellular Young's modulus and morphology) until the resulting multi-cellular stage (indicated by cellular functions) through distinguished proliferative patterns. Epithelial cells on soft substrate proliferated in a neighbor-dependent manner with stronger E-cadherin expression and more homogeneous E-cadherin/β-catenin localization compared to those on coverslips, which resulted in reduced heterogeneity in downstream cellular functions of the multi-cellular population. In particular, decreased heterogeneity in human embryonic stem cells upon expansion and endodermal induction was achieved on soft substrate. Overall, our work provides new insights on mechanotransduction during epithelial proliferation which regulates the formation of cellular heterogeneity and potentially provides a highly efficient approach to regulate stem cell fate by fine-tuning substrate stiffness. STATEMENT OF SIGNIFICANCE:This study demonstrates that cellular heterogeneity regulated by substrate stiffness is evident starting from the initial single-cell stage until the resulting multi-cellular stage through distinguished proliferative patterns. During this process, E-cadherin/β-catenin mechanotransduction is found to play important role in substrate stiffness-regulated epithelial cellular heterogeneity formation. In particular, decreased heterogeneity in human embryonic stem cells upon expansion and endodermal induction is achieved on soft substrate. Hence, we believe that this work not only provides new insights on mechanotransduction of E-cadherin/β-catenin which regulates the formation of cellular heterogeneity during proliferation, but also potentially provides a highly efficient approach to regulate stem cell fate by fine-tuning substrate stiffness.
journal_name
Acta Biomaterjournal_title
Acta biomaterialiaauthors
Wang B,Qin P,Zhao H,Xia T,Wang J,Liu L,Zhu L,Xu J,Huang C,Shi Y,Du Ydoi
10.1016/j.actbio.2016.05.025subject
Has Abstractpub_date
2016-09-01 00:00:00pages
169-80eissn
1742-7061issn
1878-7568pii
S1742-7061(16)30243-4journal_volume
41pub_type
杂志文章abstract::Antibiotic resistance of bacterial biofilms limits available treatment methods for implant-associated orthopaedic infections. This study evaluated the effects of applying cathodic voltage-controlled electrical stimulations (CVCES) of -1.5V and -1.8V (vs. Ag/AgCl) to coupons of commercially pure titanium (cpTi) incubat...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2016.11.056
更新日期:2017-01-15 00:00:00
abstract::The boundary layers coating articular cartilage in synovial joints constitute unique biomaterials, providing lubricity at levels unmatched by any human-made materials. The underlying molecular mechanism of this lubricity, essential to joint function, is not well understood. Here we study the interactions between surfa...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2017.06.043
更新日期:2017-09-01 00:00:00
abstract::Eggshell membrane (ESM) is a unique biomaterial, which is generally considered as waste. However, it has extraordinary properties which can be utilized in various fields and its potential applications are therefore now being widely studied. The first part of this review focuses on the chemical composition and morpholo...
journal_title:Acta biomaterialia
pub_type: 杂志文章,评审
doi:10.1016/j.actbio.2014.03.020
更新日期:2014-09-01 00:00:00
abstract::Thrombus formation, due to thrombin generation, is a major problem affecting blood-contacting medical devices. This work aimed to develop a new strategy to improve the hemocompatibility of such devices by the immobilization of a naturally occurring thrombin inhibitor into a nanostructured surface. Boophilin, a direct ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2012.07.020
更新日期:2012-11-01 00:00:00
abstract:UNLABELLED:Quercetin (3,3',4',5,7-pentahydroxy-flavone) is a flavonoid known for its pharmacological activities, which include antioxidant and anti-inflammatory properties, as well as possible beneficial action on diseases involving bone loss. In this work, we explored the possibility to functionalize hydroxyapatite (H...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2015.12.013
更新日期:2016-03-01 00:00:00
abstract::Successful osteochondral defect repair requires regenerating the subchondral bone whilst simultaneously promoting the development of an overlying layer of articular cartilage that is resistant to vascularization and endochondral ossification. During skeletal development articular cartilage also functions as a surface ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2020.05.040
更新日期:2020-09-01 00:00:00
abstract::The present study focuses on apatite coating on collagen films, with various different densities of carboxyl groups, using an alternate soaking process. Anionic collagen (AC), which has different densities of carboxylic groups compared to native collagen (NC), was obtained by hydrolysis of carboxyamides of asparagine ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2007.02.008
更新日期:2007-09-01 00:00:00
abstract::Decellularized extracellular matrix (ECM) derived from stem cells has been shown as a promising biomaterial for bone regeneration because of the promotion effect on osteogenesis in mesenchymal stem cells (MSCs). However, bone regeneration is also influenced by bone resorption and little is known about the effect of ce...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2018.03.003
更新日期:2018-04-15 00:00:00
abstract::A three-dimensional (3-D) cell culture system that allows control of both substrate stiffness and integrin binding density was created and characterized. This system consisted of two self-assembling peptide (SAP) sequences that were mixed in different ratios to achieve the desired gel stiffness and adhesiveness. The s...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2013.04.002
更新日期:2013-08-01 00:00:00
abstract::The specific aim of this study was to gain insight into the influence of scaffold pore size, pore shape and permeability on the in vitro proliferation and differentiation of three-dimensional (3-D) human periosteum-derived cell (hPDC) cultures. Selective laser melting (SLM) was used to produce six distinct designed ge...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2012.04.001
更新日期:2012-07-01 00:00:00
abstract::Crystalline Mg-Zinc (Zn)-Strontium (Sr) ternary alloys consist of elements naturally present in the human body and provide attractive mechanical and biodegradable properties for a variety of biomedical applications. The first objective of this study was to investigate the degradation and cytocompatibility of four Mg-4...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2016.10.020
更新日期:2017-01-15 00:00:00
abstract::Surgical suture is a strand of biocompatible material designed for wound closure, and therefore can be a medical device potentially suitable for local drug delivery to treat pain at the surgical site. However, the preparation methods previously introduced for drug-delivery sutures adversely influenced the mechanical s...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2013.06.003
更新日期:2013-09-01 00:00:00
abstract::Calcium phosphate based bioceramics have been widely used for orthopedic applications due to their chemical similarity to natural bone. The Ca/P stoichiometry of calcium phosphates strongly influences their performance under biological conditions, which have not yet been fully elucidated to date. For this reason, the ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2008.02.025
更新日期:2008-09-01 00:00:00
abstract::We present a systematic study for investigating the role of exposed hydroxyapatite (HA) nanoparticles in influencing surface characteristics and mouse pre-osteoblastic MC3T3-E1 cell behavior using nanocomposites prepared by photo-crosslinking poly(ε-caprolactone) diacrylate (PCLDA) with HA. PCLDA530 and PCLDA2000 synt...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2011.01.034
更新日期:2011-05-01 00:00:00
abstract::The influence of ionic substituents in calcium phosphates intended for bone and tooth replacement biomedical applications is an important research topic, owing to the essential roles played by trace elements in biological processes. The present study investigates the mechanical and biological evaluation of ionic doped...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2010.12.009
更新日期:2011-04-01 00:00:00
abstract::Vascular damage develops with diverging severity during and after percutaneous coronary intervention with stent placement and is the prevailing stimulus for in-stent restenosis. Previous work has failed to link mechanical data obtained in a realistic in vivo or in vitro environment with data collected during imaging p...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2020.08.016
更新日期:2020-10-15 00:00:00
abstract::Bioactive ions released from bioceramics play important roles in bone regeneration; however, it is unclear how each ionic composition in complex bioceramics exerts its specific effect on bone regeneration. The aim of this study is to elucidate the functional effects of Sr and Si ions in bioceramics on the regeneration...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2017.08.015
更新日期:2017-10-01 00:00:00
abstract::This study concerns the preparation and in vitro characterization of an apatite-wollastonite-2M bioactive glass ceramic which is intended to be used for the regeneration of hard tissue (i.e. in dental and craniomaxillofacial surgery). This bioglass ceramic has been obtained by appropriate thermal treatment through the...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.12.027
更新日期:2010-06-01 00:00:00
abstract::Due to the prevalence of problems caused by wear particles, the reduced durability of total joint replacements is well documented. The characterization of wear debris enables the size and morphology of these wear particles to be measured and provides an assessment of the biological response in vivo. However, the impac...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2013.07.039
更新日期:2013-12-01 00:00:00
abstract::Stink bugs have wing coupling mechanisms to synchronize flapping of their wings. The wing coupling is performed through a clamp-like structure on the fore wing (i.e. hemelytron) and a rolled margin on the hind wing. Here we used modern imaging techniques to investigate structural characteristics and material compositi...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2019.09.027
更新日期:2019-12-01 00:00:00
abstract::A novel bactericidal material comprising rod-shaped core-shell-shell Au-Ag-Au nanorods is constructed as a nanoheater in the near-infrared (NIR) region. The outer Au shell melts under laser irradiation and results in exposure of the inner Ag shell, facilitating the controlled release of the antibacterial Ag shell/laye...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2014.09.005
更新日期:2015-01-01 00:00:00
abstract::Nano-crystalline Zn-containing hydroxyapatite (ZnHAp) was prepared by the wet-chemical method and the selective adsorption of essential proteins was examined, taking bovine serum albumin (BSA) and pathogenic protein such as beta(2)-microglobulin (beta(2)-MG) as model proteins. Transmission electron microscopy observat...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2005.09.002
更新日期:2006-01-01 00:00:00
abstract::The lifetime and stability of insulation are critical features for the reliable operation of an implantable neural interface device. A critical factor for an implanted insulation's performance is its barrier properties that limit access of biological fluids to the underlying device or metal electrode. Parylene C is a ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2013.10.031
更新日期:2014-02-01 00:00:00
abstract::This work focuses on the synthesis and characterization of a novel bioresorbable glass ceramic phosphate-based material (GC-ICEL). More specifically, its solubility in different aqueous media (water, Tris-HCl and acellular simulated body fluid) and the response of human stromal cells cultured on it were investigated. ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.07.017
更新日期:2010-02-01 00:00:00
abstract::Wound infections are a significant clinical problem affecting millions of people worldwide. Topically applied antibacterial formulations with longer residence time and controlled antimicrobial release would offer significant benefits for improved prevention and treatment of infected wounds. In this study, we developed...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2019.12.014
更新日期:2020-02-01 00:00:00
abstract::The main objective of this study was to investigate calcium phosphate (CaP) coatings on Ti6Al4V substrates by using the biomimetic technique. To this purpose, a new solution was developed to coat CaP on Ti6Al4V alloy substrates. The newly formulated body fluid (Lac-SBF) contained appropriate amounts of sodium lactate ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.12.013
更新日期:2010-06-01 00:00:00
abstract::The macrophysical properties of granular biomaterials used to fill bone defects have rarely been considered. Granules of a given biomaterial occupy three-dimensional (3-D) space when packed together and create a macroporosity suitable for the invasion of vascular and bone cells. Granules of β-tricalcium phosphate were...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2014.09.015
更新日期:2015-01-01 00:00:00
abstract::Dental-derived mesenchymal stem cells (MSCs) are promising candidates for cartilage regeneration, with a high capacity for chondrogenic differentiation. This property helps make dental MSCs an advantageous therapeutic option compared to current treatment modalities. The MSC delivery vehicle is the principal determinan...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2013.07.023
更新日期:2013-12-01 00:00:00
abstract::Cell transplantation therapies to treat diseases related to dysfunction of retinal ganglion cells (RGCs) are limited in part by an inability to navigate to the optic nerve head within the retina. During development, RGCs are guided by a series of neurotrophic factors and guidance cues; however, these factors and their...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2014.08.032
更新日期:2014-12-01 00:00:00
abstract::Surface functionalization has become of paramount importance and is considered a fundamental tool for the development and design of countless devices and engineered systems for key technological areas in biomedical, biotechnological and environmental applications. In this review, surface functionalization strategies f...
journal_title:Acta biomaterialia
pub_type: 杂志文章,评审
doi:10.1016/j.actbio.2013.03.036
更新日期:2013-07-01 00:00:00