Mechanics of collective unfolding

Mechanically induced unfolding of passive crosslinkers is a fundamental biological phenomenon encountered across the scales from individual macro-molecules to cytoskeletal actin networks. In this paper we study a conceptual model of athermal load-induced unfolding and use a minimalistic setting allowing one to emphasize the role of long-range interactions while maintaining full analytical transparency. Our model can be viewed as a description of a parallel bundle of N bistable units confined between two shared rigid backbones that are loaded through a series spring. We show that the ground states in this model correspond to synchronized, single phase configurations where all individual units are either folded or unfolded. We then study the fine structure of the wiggly energy landscape along the reaction coordinate linking the two coherent states and describing the optimal mechanism of cooperative unfolding. Quite remarkably, our study shows the fundamental difference in the size and structure of the folding-unfolding energy barriers in the hard (fixed displacements) and soft (fixed forces) loading devices which persists in the continuum limit. We argue that both, the synchronization and the non-equivalence of the mechanical responses in hard and soft devices, have their origin in the dominance of long-range interactions. We then apply our minimal model to skeletal muscles where the power-stroke in acto-myosin crossbridges can be interpreted as passive folding. A quantitative analysis of the muscle model shows that the relative rigidity of myosin backbone provides the long-range interaction mechanism allowing the system to effectively synchronize the power-stroke in individual crossbridges even in the presence of thermal fluctuations. In view of the prototypical nature of the proposed model, our general conclusions pertain to a variety of other biological systems where elastic interactions are mediated by effective backbones

Cooperative folding of muscle myosins: I. Mechanical model

Mechanically induced folding of passive cross-linkers is a fundamental biological phenomenon. A typical example is a conformational change in myosin II responsible for the power-stroke in skeletal muscles. In this paper we present an athermal perspective on such folding by analyzing the simplest purely mechanical prototype: a parallel bundle of bi-stable units attached to a common backbone. We show that in this analytically transparent model, characterized by a rugged energy landscape, the ground states are always highly coherent, single-phase configurations. We argue that such cooperative behavior, ensuring collective conformational change, is due to the dominance of long- range interactions making the system non-additive. The detailed predictions of our model are in agreement with experimentally observed non-equivalence of fast force recovery in skeletal muscles loaded in soft and hard devices. Some features displayed by the model are also recognizable in the behavior of other biological systems with passive multi-stability and long-range interactions including detaching adhesive binders and pulled RNA/DNA hairpins

Challenges of Measuring Performance of the Sales and Operations Planning Process

The purpose of this study is to identify and structure challenges of measuring performance of the Sales and Operations Planning (S&OP) process. A multiple case study methodology was applied. Qualitative data was collected via 22 structured interviews with managers from six case companies in various industries. A process oriented framework was proposed by structuring the challenges based on two key areas of process performance (effectiveness and efficiency) and different maturity levels of the process. A major challenge for all the cases, regardless of their maturity level, relates to defining of cross-functional trade-offs measures. Another major challenge was alignment of measures with business strategy and reward system. Additional common challenges for the different maturity levels were also found. While confirming some challenges from previous research, this study also finds new challenges, especially for more mature levels. Examples are standardization to support unbiased decision making, but also customization of measures for various organizational levels, and visualization of findings from the measurement to facilitate analysis. However, future research must validate and extend the results in other industries. The results offer challenges from a process oriented view and can serve as insights for managers when designing and implementing the S&OP process measures, or advancing from one maturity level to another. This research enhances understanding of the challenges to measure the S&OP process performance and adds to the S&OP literature and performance measurement literature

Cooperative folding of muscle myosins: I. Mechanical model

Mechanically induced folding of passive cross-linkers is a fundamental biological phenomenon. A typical example is a conformational change in myosin II responsible for the power-stroke in skeletal muscles. In this paper we present an athermal perspective on such folding by analyzing the simplest purely mechanical prototype: a parallel bundle of bi-stable units attached to a common backbone. We show that in this analytically transparent model, characterized by a rugged energy landscape, the ground states are always highly coherent, single-phase configurations. We argue that such cooperative behavior, ensuring collective conformational change, is due to the dominance of long- range interactions making the system non-additive. The detailed predictions of our model are in agreement with experimentally observed non-equivalence of fast force recovery in skeletal muscles loaded in soft and hard devices. Some features displayed by the model are also recognizable in the behavior of other biological systems with passive multi-stability and long-range interactions including detaching adhesive binders and pulled RNA/DNA hairpins