Membrane fluidity matters: Hyperthermia from the aspects of lipids and membranes

Hyperthermia is a promising treatment modality for cancer in combination both with radio- and chemotherapy. In spite of its great therapeutic potential, the underlying molecular mechanisms still remain to be clarified. Due to lipid imbalances and 'membrane defects' most of the tumour cells possess elevated membrane fluidity. However, further increasing membrane fluidity to sensitise to chemo-or radiotherapy could have some other effects. In fact, hyperfluidisation of cell membrane induced by membrane fluidiser initiates a stress response as the heat shock protein response, which may modulate positively or negatively apoptotic cell death. Overviewing some recent findings based on a technology allowing direct imaging of lipid rafts in live cells and lipidomics, novel aspects of the intimate relationship between the 'membrane stress' of tumour cells and the cellular heat shock response will be highlighted. Our findings lend support to both the importance of membrane remodelling and the release of lipid signals initiating stress protein response, which can operate in tandem to control the extent of the ultimate cellular thermosensitivity. Overall, we suggest that the fluidity variable of membranes should be used as an independent factor for predicting the efficacy of combinational cancer therapies

Membrane repair and immunological danger

Antigens are able to elicit productive immune responses only when second signals are provided by adjuvant molecules. It is well established that exogenously acquired, pathogen-associated molecular patterns fulfil this adjuvant role when recognized by specific receptors on antigen-presenting cells. Recent evidence points to the existence of another class of adjuvant, which is apparently released from injured cells. Such endogenous adjuvants, referred to as 'danger' signals, could alert the immune system to situations that cause cell damage, but not necessarily those that involve infections. Endogenous adjuvants provide a good explanation for immune responses generated against tumours and autologous tissues, but it has been difficult to explain how a constant activation of the immune system is avoided, considering the frequency at which cells are injured in vivo. Here, we suggest that the efficiency with which cells reseal wounds in their plasma membrane might be an important factor in the balance between tolerance and autoimmunity. Recent observations in synaptotagmin-VII-deficient mice suggest that defective membrane repair could lead to autoimmunity in tissues that are more susceptible to mechanical injury