Phytochemicals Perturb Membranes and Promiscuously Alter Protein Function

A wide variety of phytochemicals are consumed for their perceived health benefits. Many of these phytochemicals have been found to alter numerous cell functions, but the mechanisms underlying their biological activity tend to be poorly understood. Phenolic phytochemicals are particularly promiscuous modifiers of membrane protein function, suggesting that some of their actions may be due to a common, membrane bilayer-mediated mechanism. To test whether bilayer perturbation may underlie this diversity of actions, we examined five bioactive phenols reported to have medicinal value: capsaicin from chili peppers, curcumin from turmeric, EGCG from green tea, genistein from soybeans, and resveratrol from grapes. We find that each of these widely consumed phytochemicals alters lipid bilayer properties and the function of diverse membrane proteins. Molecular dynamics simulations show that these phytochemicals modify bilayer properties by localizing to the bilayer/solution interface. Bilayer-modifying propensity was verified using a gramicidin-based assay, and indiscriminate modulation of membrane protein function was demonstrated using four proteins: membrane-anchored metalloproteases, mechanosensitive ion channels, and voltage-dependent potassium and sodium channels. Each protein exhibited similar responses to multiple phytochemicals, consistent with a common, bilayer-mediated mechanism. Our results suggest that many effects of amphiphilic phytochemicals are due to cell membrane perturbations, rather than specific protein binding

Der Ambivalenzbegriff in Carl Friedrich von Weizsäckers Starnberger Institutskonzept

The strong impetus towards self-reflection of science during the 1960ies culminated around 1970 in the foundation of many relevant research institutions in different countries. Although included into that general trend, the MPI for the Exploration of Living Conditions in the Sci-entific-Technological World at Starnberg, established under the direction of Carl Friedrich von Weizsäcker in 1970, pursued a unique idea, somewhat apart from the mainstream charac-terizing most institutes in the emerging field of science research (science of science, science studies, social studies of science, etc.). Meanwhile science research usually was focused on science as a sub-system of modern societies, for the Starnberg institute the typical subject was the “scientific-technological world” – mankind in global context increasingly based on sci-ence as a leading source of innovation and evolution. As a key concept for describing and analyzing the living conditions in the scientific-technological world, von Weizsäcker employs the idea of ambivalence. Obviously it means a proto-theoretical, fuzzy concept that cannot be introduced explicitly per definition; starting with an intuitive perception, “ambivalence” should gradually gain meaning by using it in dif-ferent argumentative contexts. Following a circular course (Kreisgang) – a procedure typical for von Weizsäcker’s style of thought – , he moves successively from explicit ambivalence in the application sphere of science through ambivalent features in scientists’ behaviour and ac-tion up to the general ambivalence of human existence prior to rationality and science, dis-closed at an anthropological level of deliberation situated between philosophy and common sense. He criticized profoundly the wide-spread conviction about the alleged neutrality of science becoming ambivalent only due to application under contrary goals; von Weizsäcker’s approach allowed to overcome the essentially inadequate and ethically questionable opinion mentioned above and to understand scientific cognition even at the level of “pure science” as an ambivalent enterprise. The given paper mainly discusses an essay by von Weizsäcker written in the starting year of the Starnberg institute (October 1970) under the title “Living conditions, Reflection on the interrelation of subjects”. The essay was a response to many conceptual proposals, presented by his (mostly young) scientific co-workers, and intended, at the same time, to inspire further discussion about the future profile of the institute. Von Weizsäcker’s remarkable effort to pay attention to the different ideas of his collaborators and to fit them into a more general network gave him reason to sketch a complex conceptual structure capable to integrate a broad range of suggestions; so the concept of ambivalence may be characterized as an indispensable mo-ment of central importance in the intellectual architecture of the Starnberg institute

Zur Entwicklung der biologischen Disziplinen in Berlin insbesondere an der Berliner Universitaet

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