Biophysical mechanisms of single-cell interactions with microtopographical cues

Biophysical cues encoded in the extracellular matrix (ECM) are increasingly being explored to control cell behavior in tissue engineering applications. Recently, we showed that cell adhesion to microtopographical structures (“micropegs”) can suppress proliferation in a manner that may be blunted by inhibiting cellular contractility, suggesting that this effect is related to altered cell-scaffold mechanotransduction. We now directly investigate this possibility at the microscale through a combination of live-cell imaging, single-cell mechanics methods, and analysis of gene expression. Using time-lapse imaging, we show that when cells break adhesive contacts with micropegs, they form F-actin-filled tethers that extend and then rupture at a maximum, critical length that is greater than trailing-edge tethers observed on topographically flat substrates. This critical tether length depends on myosin activation, with inhibition of Rho-associated kinase abolishing topography-dependent differences in tether length. Using cellular de-adhesion and atomic force microscopy indentation measurements, we show that the micropegs enhance cell-scaffold adhesive interactions without changing whole-cell elasticity. Moreover, micropeg adhesion increases expression of specific mechanotransductive genes, including RhoA GTPase and myosin heavy chain II, and, in myoblasts, the functional marker connexin 43. Together, our data support a model in which microtopographical cues alter the local mechanical microenvironment of cells by modulating adhesion and adhesion-dependent mechanotransductive signaling

Strategies to facilitate implementation and sustainability of large system transformations : a case study of a national program for improving quality of care for elderly people

BACKGROUND: Large-scale change initiatives stimulating change in several organizational systems in the health and social care sector are challenging both to lead and evaluate. There is a lack of systematic research that can enrich our understanding of strategies to facilitate large system transformations in this sector. The purpose of this study was to examine the characteristics of core activities and strategies to facilitate implementation and change of a national program aimed at improving life for the most ill elderly people in Sweden. The program outcomes were also addressed to assess the impact of these strategies. METHODS: A longitudinal case study design with multiple data collection methods was applied. Archival data (n = 795), interviews with key stakeholders (n = 11) and non-participant observations (n = 23) were analysed using content analysis. Outcome data was obtained from national quality registries. RESULTS: This study presents an approach for implementing a large national change program that is characterized by initial flexibility and dynamism regarding content and facilitation strategies and a growing complexity over time requiring more structure and coordination. The description of activities and strategies show that the program management team engaged a variety of stakeholders and actor groups and accordingly used a palate of different strategies. The main strategies used to influence change in the target organisations were to use regional improvement coaches, regional strategic management teams, national quality registries, financial incentives and annually revised agreements. Interactive learning sessions, intense communication, monitor and measurements, and active involvement of different experts and stakeholders, including elderly people, complemented these strategies. Program outcomes showed steady progress in most of the five target areas, less so for the target of achieving coordinated care. CONCLUSIONS: There is no blue-print on how to approach the challenging task of leading large scale change programs in complex contexts, but our conclusion is that more attention has to be given to the multidimensional strategies that program management need to consider. This multidimensionality comprises different strategies depending on types of actors, system levels, contextual factors, program progress over time, program content, types of learning and change processes, and the conditions for sustainability