Fig. 6: Model of C. albicans trans-cellular tunnelling (CaTCT).

A model based on the hypothesis that host membranes extend from each invaded cell into the next host cell in the invasion sequence, resulting in progressive membrane layer accumulation. Alternatively, additional membrane layers may be recruited from internal host endocytic compartments or formed de novo in each invaded cell in correspondence with the invasion sequence, though we reason these are less likely possibilities (see Discussion). These latter models are not presented. I Invasion into the first cell in the invasion sequence (cell 1) is characterized by tight enveloping by the cell 1 plasma membrane as well as an ‘exclusion layer’ (EL), likely containing actin derived from the apical actin cortex. II At the onset of invasion into the second cell in the sequence (cell 2), the structures surrounding the hypha in cell 1, i.e. cell 1 plasma membrane (added during cell 1 entry), and another cell 1 plasma membrane (added during cell 1 exit), are enveloped by the plasma membrane of cell 2. Parts of the exclusion layer in cell 1 may possibly also extend into the TCT structure (grey dots). III Invasion into cell 3 proceeds in a similar manner, with the structures surrounding the hypha in cell 2 enveloped by the plasma membrane of cell 3. Cross-section views (derived from dotted lines) show the membrane layers surrounding the hypha cell wall (black), with the exclusion layer in dark grey, and each membrane layer coloured according to its cell of origin, i.e. magenta- cell 1, green- cell 2, yellow- cell 3. Additional actin layers derived from non-apical cortical actin may also be present within the TCT structure, but they were not illustrated for clarity. The model presented applies to non-damaging invasion, and does not account for scenarios where host membrane breaching occurs.