Dynamic Micropatterning Reveals Substrate-Dependent Differences in the Geometric Control of Cell Polarization and Migration

Cells are highly dynamic and adopt variable shapes and sizes. These variations are biologically important but challenging to investigate in a spatiotemporally controlled manner. Micropatterning, confining cells on microfabricated substrates with defined geometries and molecular compositions, is a powerful tool for controlling cell shape and interactions. However, conventional binary micropatterns are static and fail to address dynamic changes in cell polarity, spreading, and migration. Here, a method for dynamic micropatterning is reported, where the non-adhesive surface surrounding adhesive micropatterns is rapidly converted to support specific cell-matrix interactions while allowing simultaneous imaging of the cells. The technique is based on ultraviolet photopatterning of biotinylated polyethylene glycol-grafted poly-L-lysine, and it is simple, inexpensive, and compatible with a wide range of streptavidin-conjugated ligands. Experiments using biotinylation-based dynamic micropatterns reveal that distinct extracellular matrix ligands and bivalent integrin-clustering antibodies support different degrees of front-rear polarity in human glioblastoma cells, which correlates to altered directionality and persistence upon release and migration on fibronectin. Unexpectedly, however, neither an asymmetric cell shape nor centrosome orientation can fully predict the future direction of migration. Taken together, biotinylation-based dynamic micropatterns allow easily accessible and highly customizable control over cell morphology and motility

Integrin signaling and mechanotransduction in regulation of somatic stem cells

Somatic stem cells are characterized by their capacity for self-renewal and differentiation, making them integral for normal tissue homeostasis. Different stem cell functions are strongly affected by the specialized micro-environment surrounding the cells. Consisting of soluble signaling factors, extracellular matrix (ECM) ligands and other cells, but also biomechanical cues such as the viscoelasticity and topography of the ECM, these factors are collectively known as the niche. Cell-ECM interactions are mediated largely by integrins, a class of heterodimeric cell adhesion molecules. Integrins bind their ligands in the extracellular space and associate with the cytoskeleton inside the cell, forming a direct mechanical link between the cells and their surroundings. Indeed, recent findings have highlighted the importance of integrins in translating biophysical cues into changes in cell signaling and function, a multistep process known as mechanotransduction. The mechanical properties of the stem cell niche are important, yet the underlying molecular details of integrin-mediated mechanotransduction in stem cells, especially the roles of the different integrin heterodimers, remain elusive. Here, we introduce the reader to the concept of integrin-mediated mechanotransduction, summarize current knowledge on the role of integrin signaling and mechanotransduction in regulation of somatic stem cell functions, and discuss open questions in the field

Connected Health User Willingness to Share Personal Health Data: Questionnaire Study

Abstract Background: Connected health has created opportunities for leveraging health data to deliver preventive and personalized health care services. The increasing number of personal devices and advances in measurement technologies contribute to an exponential growth in digital health data. The practices for sharing data across the health ecosystem are evolving as there are more opportunities for using such data to deliver responsive health services. Objective: The objective of this study was to explore user attitudes toward sharing personal health data (PHD). The study was executed within the first year after the implementation of the new General Data Protection Regulation (GDPR) legal framework. Methods: The authors analyzed the results of an online questionnaire survey to explore the willingness of 8004 people using connected health services across four European countries to share their PHD and the conditions under which they would be willing to do so. Results: Our findings indicate that the majority of users are willing to share their personal PHD for scientific research (1811/8004, 22.63%). Age, education level, and occupation of the participants, in addition to the level of digitalization in their country were found to be associated with data sharing attitudes. Conclusions: Positive attitudes toward data sharing for scientific research can be perceived as an indication of trust established between users and academia. Nevertheless, the interpretation of data sharing attitudes is a complex process, related to and influenced by various factors

Mechano-responsiveness of fibrillar adhesions on stiffness-gradient gels

Fibrillar adhesions are important structural and adhesive components in fibroblasts, and are required for fibronectin fibrillogenesis. While nascent and focal adhesions are known to respond to mechanical cues, the mechanoresponsive nature of fibrillar adhesions remains unclear. Here, we used ratiometric analysis of paired adhesion components to determine an appropriate fibrillar adhesion marker. We found that active α5β1-integrin exhibits the most definitive fibrillar adhesion localization compared to other proteins, such as tensin-1, reported to be in fibrillar adhesions. To elucidate the mechanoresponsiveness of fibrillar adhesions, we designed a cost-effective and reproducible technique to fabricate physiologically relevant stiffness gradients on thin polyacrylamide (PA) hydrogels, embedded with fluorescently labelled beads. We generated a correlation curve between bead density and hydrogel stiffness, thus enabling a readout of stiffness without the need for specialized knowhow, such as atomic force microscopy (AFM). We find that stiffness promotes growth of fibrillar adhesions in a tensin-1-dependent manner. Thus, the formation of these extracellular matrix-depositing structures is coupled to the mechanical parameters of the cell environment and may enable cells to fine-tune their matrix environment in response to changing physical conditions

Convergent communication, sensing and localization in 6g systems: An overview of technologies, opportunities and challenges

Herein, we focus on convergent 6G communication, localization and sensing systems by identifying key technology enablers, discussing their underlying challenges, implementation issues, and recommending potential solutions. Moreover, we discuss exciting new opportunities for integrated localization and sensing applications, which will disrupt traditional design principles and revolutionize the way we live, interact with our environment, and do business. Regarding potential enabling technologies, 6G will continue to develop towards even higher frequency ranges, wider bandwidths, and massive antenna arrays. In turn, this will enable sensing solutions with very fine range, Doppler, and angular resolutions, as well as localization to cm-level degree of accuracy. Besides, new materials, device types, and reconfigurable surfaces will allow network operators to reshape and control the electromagnetic response of the environment. At the same time, machine learning and artificial intelligence will leverage the unprecedented availability of data and computing resources to tackle the biggest and hardest problems in wireless communication systems. As a result, 6G will be truly intelligent wireless systems that will provide not only ubiquitous communication but also empower high accuracy localization and high-resolution sensing services. They will become the catalyst for this revolution by bringing about a unique new set of features and service capabilities, where localization and sensing will coexist with communication, continuously sharing the available resources in time, frequency, and space. This work concludes by highlighting foundational research challenges, as well as implications and opportunities related to privacy, security, and trust

Convergent Communication, Sensing and Localization in 6G Systems: An Overview of Technologies, Opportunities and Challenges

Herein, we focus on convergent 6G communication, localization and sensing systems by identifying key technology enablers, discussing their underlying challenges, implementation issues, and recommending potential solutions. Moreover, we discuss exciting new opportunities for integrated localization and sensing applications, which will disrupt traditional design principles and revolutionize the way we live, interact with our environment, and do business. Regarding potential enabling technologies, 6G will continue to develop towards even higher frequency ranges, wider bandwidths, and massive antenna arrays. In turn, this will enable sensing solutions with very fine range, Doppler, and angular resolutions, as well as localization to cm-level degree of accuracy. Besides, new materials, device types, and reconfigurable surfaces will allow network operators to reshape and control the electromagnetic response of the environment. At the same time, machine learning and artificial intelligence will leverage the unprecedented availability of data and computing resources to tackle the biggest and hardest problems in wireless communication systems. As a result, 6G will be truly intelligent wireless systems that will provide not only ubiquitous communication but also empower high accuracy localization and high-resolution sensing services. They will become the catalyst for this revolution by bringing about a unique new set of features and service capabilities, where localization and sensing will coexist with communication, continuously sharing the available resources in time, frequency, and space. This work concludes by highlighting foundational research challenges, as well as implications and opportunities related to privacy, security, and trust

The Extent and Coverage of Current Knowledge of Connected Health: Systematic Mapping Study

Background: This paper examines the development of the Connected Health research landscape with a view on providing a historical perspective on existing Connected Health research. Connected Health has become a rapidly growing research field as our healthcare system is facing pressured to become more proactive and patient centred. Objective: We aimed to identify the extent and coverage of the current body of knowledge in Connected Health. With this, we want to identify which topics have drawn the attention of Connected health researchers, and if there are gaps or interdisciplinary opportunities for further research. Methods: We used a systematic mapping study that combines scientific contributions from research on medicine, business, computer science and engineering. We analyse the papers with seven classification criteria, publication source, publication year, research types, empirical types, contribution types research topic and the condition studied in the paper. Results: Altogether, our search resulted in 208 papers which were analysed by a multidisciplinary group of researchers. Our results indicate a slow start for Connected Health research but a more recent steady upswing since 2013. The majority of papers proposed healthcare solutions (37%) or evaluated Connected Health approaches (23%). Case studies (28%) and experiments (26%) were the most popular forms of scientific validation employed. Diabetes, cancer, multiple sclerosis, and heart conditions are among the most prevalent conditions studied. Conclusions: We conclude that Connected Health research seems to be an established field of research, which has been growing strongly during the last five years. There seems to be more focus on technology driven research with a strong contribution from medicine, but business aspects of Connected health are not as much studied